Investigation of the thionation reaction of cyclic imides

Article abstract of DOI:10.1515/znb-2001-1012

A series of monothioimides and dithioimides were synthesised using Lawesson's reagent. It has been found that two main effects affect thionation reaction. The high polarity of carbonyl groups leads to good yields of mono- and dithioimides. On the other hand, steric hindrance in the vicinity of the carbonyl group strongly inhibits the replacement of the oxygen atom by sulfur.

Full text of DOI:10.1515/znb-2001-1012

Investigation of the Thionation Reaction of Cyclic Imides
A. Orzeszko3, J. K. M aurinbc, and D. M elon-Ksyta
3
a Agricultural University, Institute of Chemistry, 02-528 Warsaw, Poland
b Institute of Atomic Energy, 05-400 Otwock-Swierk, Poland
c Drug Institute, Chelmska 30/34, 00-725 Warsaw, Poland
Reprint requests to Prof. A. Orzeszko
Z. Naturforsch. 56b, 1035-1040 (2001); received May 11, 2001
Imides, Monothioimides, Dithioimides
A series of monothioimides and dithioimides were synthesised using Lawesson’s reagent.
It has been found that two main effects affect thionation reaction. The high polarity of
carbonyl groups leads to good yields of mono- and dithioimides. On the other hand, steric
hindrance in the vicinity of the carbonyl group strongly inhibits the replacement of the oxy-
gen atom by sulfur.
Introduction
gous to the Wittig reaction, with phosphorus ylides
giving interm ediates which may be valuable in
tetrapyrrole pigment synthesis [ ].
Thioimides, contrary to other types of thiocar-
bonyl compounds, are relatively stable materials.
This prom pted us to synthesise a series of mono-
thio- and dithioimides which show interesting
thermotropic properties and open the access to a
6
Results and Discussion
Thioimides can be simply obtained from the re-
new class of liquid crystals [1], It has been recog- spective imides using Lawesson’s reagent (LR) i.e.
nized that monothioimides can be easily desulfur-
ized with Raney nickel to give the corresponding
lactams [2]. Photochemical reactions between
thioimides and alkenes involve selective cycload-
dition to the C=S bond and yield spiro-adducts
2,4-bis(4-methoxyphenyl)-l,3-dithia-2,4-diphos-
phetane-2,4-disulfide [1,2,7, ]. There has been
8
some speculation about the mechanism of the
reaction of LR with carbonyl compounds [7], The
most probable mechanism is shown in Scheme 1.
It seems that a highly reactive dithiometaphos-
phate, rather than LR itself, may be the active
thionating agent. However, according to the best
[3, 4].
Thioimides and alkoxythiophthalimides were
also used in the synthesis of phthalocyanines [5].
Thioimides undergo reaction, in a m anner analo- of our knowledge, there have been no reports on
Ar„
s.
V
= V
S
pv
2Ar — P
'
\
S'
S'
'A r
s-
Lawesson’s Reagent
Ar =
\
V 0 C H 3
S
/
°vCU N\ ------
►
I * — P-o
------
►
V
\
Ar—pf+
Ar— p +
S'
+
\
1
1
/
l
+
\
S—C -N
I
\
Scheme 1.
0932-0776/2001/1000-1035 $06.00 © 2001 Verlag der Zeitschrift für Naturforschung, Tübingen • www.znaturforsch.com
D
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1036
A. Orzeszko et al. • Investigation of the Thionation Reaction of Cyclic Imides
LR ,A , 60'
toluene
0
%-1 0 0 %
1 - 1 1
la - 11a
lb - lib
2
1
3
4
5
O
v
O
O
C
” ®
O
O
O
i
r
C
O
- " “
O C " - "
o
o
o
O
6
7
10
11
c - U L y - "
W
y
/ - »
o
L J L / t ch’
o CH’
T
i
U
r
O
c h j
^
Cl
o
the influence of the imide structure on the thiona-
tion reaction. In this paper, we show some lim ita-
tions that have appeared in the synthesis of thio-
imides.
The imides 1-11, listed in Scheme 2, were con-
verted into the respective thioimides by the reac-
tion with LR in boiling toluene. We have found
that treatm ent of imides 1, 2, 5, 8 and 10 with LR
leads to mixtures of two main products, which
form two distinct spots on TLC and could be easily
separated by column chromatography. The respec-
tive reaction yields are given in Table 1.
The products were identified by FTIR, NM R
and elem ental analysis similarly as described pre-
viously [1,2,9]. The spectral data are given in
Table 2.
The absorption bands characteristic of imide
groups in the range from 1780 to 1720 cm - 1 were
absent in the spectra of the gold-brown com-
pounds corresponding to the TLC spots with high-
est R f values. Instead, absorption bands character-
istic of C=S groups in the range 1360-1265 cm - 1
are present. Therefore we described the products
as dithioimides lb through lib. The red-orange
products corresponding to the low mobility spots
which showed both imide and thioimide absorp-
tion bands were assigned to compounds la
through 11a.
Table 1. Formal charges of carbonyl groups and yields
of thioimides.
Sub-
strate
Formal charge
+dC = O d
Yield [%]
of mono-
Yield [%]
of dithio-
imidea
thioimide
3
C
O
0.360
(0.353)b
0.361
26
6 6
1
-0.295
(-0.287)
-0.296
78
0
2
2 0
(0.355)
0.361
(-0.290)
-0.301
24
1 1
16
1 1
0
3
4
5
6
(0.360)
0.367
(-0.289)
-0.301
(-0.289)
-0.319
(-0.272)
-0.277
(-0.272)
-0.282
-0.286
(-0.284)
-0.336
(-0.325)
-0.339
(-0.323)
-0.280
(-0.273)
0
(0.360)
0.361
16
0
(0.354)
0.362
(0.354)
0.368
7
8
0
2
0
15
0.362
(0.356)
0.358
0
98
9
(0.348)
0.359
8
8
1
1
0
1 0
(0.348)
0.325
Table 1 shows that the imides 3, 4, 6, 9 and 11
give only one main product. They are the dithio-
imide 9b and the monothioimides 3a, 4a, 6a, 11a,
respectively. A^-(r-Butyl)-3,6-dichlorophthalimide
1
53
0
(0.320)
aExpressed as a consumption of Lawesson’s Reagent;
b in parantheses are given formal charges calculated for
monothioimides (a).
(7),
(2-?-butyl-4,7-dichloro-isoindole-l,3-dione)
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A. Orzeszko et al. • Investigation of the Thionation Reaction of Cyclic Imides_______________________________ 1037
Table 2. Melting points and spectroscopic data of monothio- (a) and dithioimides (b).
Com-
pound
m.p. [°C]
'H NMR (CDCI
3
): <3, /(Hz)
FTIR
CO
(KBr) v [cm *]
CS
la
lb
2a
2b
3a
4a
5a
5b
6a
8a
7.66 (m, 2H, C
8.19 (m, 1H, C
7.45 (m, 2H, C
6
6
6
H4), 7.93 (m, 1H, C
H4), 10.30 (s, 1H, N -H )
H4), 8.24 (m, 2H, C H4),
6
H4),
1297,
1322
176 (lit. 174) [11]
1742
6
198 (lit. 184) [10, 11]
13.31 (s, 1H, N -H )
3.46 (s, 3H, CH,), 7.77 (m, 3H, C
6
H4),
H4),
1737
1322
102 (lit. 94) [2]
7.96 (m, 1H, C H4)
6
3.76 (s, 3H, CH,), 7.60 (m, 1H, C
7.72 (m, 2H, C H4)
2.85-1.71 (m, 15H, adam.), 7.62 (m, 3H,
H4), 7.87 (m, 1H, C H4)
5. 11 (s, 9H, CH,), 7.73 (m, 2H, C
7.87 (m, 1H, C H4), 7.91 (m, 1H, C
7.34-7.18 (m, 5H, C H5), 7.86 (m, 3H,
6
1323
107 (lit. 104) [5]
6
1747
1742
1747
134
1256
C
6
6
6
H4),
H4)
1311
115
6
6
6
1302
140
C
6
H4), 8.12 (m, 1H, C
6
H4)
6.89 (m, 1H, C
7.68 (m, 2H, C
6
H^), 7.20 (m, 4H, C
H4), 8.16 (m, 2H, C
6
6
H5),
H4)
1298
156
6
7.60 (d,2J=
8
.6
, 1H, C
6
H,), 7.67 (d, 2/=
8
.6
,
1745
1754
1262
250-252
201-204
1H, C
6
H2), 8.83 (s, 1H, N -H )
7.88 (s, 1H, C
6
H2), 8.04 (s, 1H, C
6
H2), 8.85
1268
(s, 1H, N -H )
8b
9b
7.95 (s, 2H, C
6
H2), 9.75 (s, 1H, N -H )
1270
1265
212-215
296-299
7.45 (m, 2H, C1 0 H6), 7.99 (m, 2H, C10 H6),
8.78 (m, 2H, C1 0 Hfi), 9.40 (s, 1H, N -H )
3,66 (s, 3H, CH,), 7.80 (m, 5H, C1 0 H6),
10a
10b
11a
218-219
302-306
82
1685
1732
1286
1291
1342
8.73 (m, 1H, C (,H6)
1
4.16 (s, 3H, CH,), 7.56 (m, 2H, C10 H6),
7.99 (m, 2H, C1 0 H6), 8.60 (m, 2H, C10 H6)
3.35 (s, 3H, CH,), 8.22 (d, 2J= 5.8, 1H,
C
2
H2), 9.66 (d, 2J= 5.8, 1H, C H2)
2
does not react with LR at all. The yields of thiona- ides, they yield quite different amounts of pro-
tion reactions differ substantially. These pheno-
mena could be explained in two ways: The m echa- methylphthalimide
ducts. The unsubstituted phthalimide 1 and N-
are easily converted quanti-
2
nism shown in Scheme 1 suggests that the polarity
of the carbonyl group should play an im portant
role in this reaction. In Table 1 the formal charges
calculated for carbonyl groups of the starting
imides and, in parentheses of the respective mono-
tatively into both monothio- and dithioimides.
Substrates with large N-substituents, 3 and 4, give
only small amounts of monothio- derivatives, and
in the case of N-phenylphthalimide 5 monothio-
and dithioimide. Also, isomers
6
and
8
react dif-
, but
thioimides are given. The naphthalimides 9 and 10, ferently. Chlorine atoms in position 3 and
6
possessing the most polar carbonyl bands, react
with LR almost quantitatively and give mainly
dithioimides. Af-methylmaleimide 11, the substrate
with the least polar C = 0 bonds, forms only the
monothioimide with 53% yield. The replacem ent
of one of the carbonyl oxygen atoms by sulfur
not in positions 4 and 5, exert a steric hindrance
which inhibits thionation reactions. As m entioned
above, the most significant effect appears for N-(t-
butyl)-3,6-dichlorophthalimide 7. In this case the
r-butyl group and the two chlorine atoms in the
vicinity of the carbonyl groups suppress thiona-
does not influence the polarity of the second car- tion completely.
bonyl group.
The different reactivity of phthalimides, naph-
The polarity of the C = 0 groups is not the only
factor determining the thionation reaction. While
thalimides and maleimide could be explained as a
result of different formal charges in their carbonyl
groups, but the different reactivity of the reported
compounds
1
and
2
have partial charges similar to
Af-(adamant-l-yl) and N-(f-butyl) substituted im- group of imides might be ascribed to the steric
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1038
A. Orzeszko et al. • Investigation of the Thionation Reaction of Cyclic Imides
effects. Despite being intuitively predictable, this
behaviour needs to be studied more closely. We
decided, therefore, to investigate the crystal struc-
tures of some imide substrates and their thiona-
pound 3 are not equivalent and that the thionation
occurs in the less crowded position. The first state-
m ent could be verified comparing O l - C l l and
0 2 ■••C15 non-bonded distances in all three mole-
tion products. Because the structure of the 7V-phe- cules shown in Fig. 1. The m ean 0 1 --C 1 1 dis-
nylphthalimide 5, as well as jV-(p-tolyl)phthal-
imide were known [12,13], we decided to study the
case of N-(t-butyl)- and N-(adam ant-l-yl)phthal-
tance is 2.769 A whereas the m ean 0 2 - C 1 5 dis-
tance is 3.050 A. The second statem ent is derived
from Figures 2 and 3. The respective O - C dis-
imide. Crystals of 3, 3a and 4a were obtained and tances in the 3a and 4a structures are even shorter
X-ray diffraction data were collected (Table 3).
In Fig. 1 the independent part of the unit cell
for 3 is shown. It consists of 1.5 molecules and
more exactly 3 halves of similar molecules. Each
molecule lies in a special position on the mirror
plane passing through the phthalimide fragments,
four carbon and two hydrogen atoms of the ada-
mantyl group.
(2.720 and 2.691 A, respectively).
In contrast to compounds 3 and 4, the carbonyl
positions in 5 are fully equivalent. In the crystal
structure of 5 [13], the phenyl ring is rotated by
58.2° with respect to the phthalim ide moiety. This
inclination corresponds to 0 1 (0 2 ) - C distances
of 3.118 and 3.177 A, respectively. This in our
opinion explains, why in the case of 5 both mono-
and dithioderivatives are obtained. A similar ef-
fect was observed for a-substituted aliphatic im-
Molecules 3a and 4a are shown in Fig. 2 and
3, respectively. Closer inspection of the drawings
shows that the carbonyl oxygen atoms in com- ides [2]. D ue to steric constrains the thionation of
Table 3. Crystal data for 3, 3a and 4a.
Compound
3
3a
4a
Empirical formula
Formula weight
Temperature
c
1 8
h
1 9 n o
2
c
1 8 h 19n o s
c
1 2 h 13n o s
281.34
100(2)K
0.71073 Ä
m
297.40
219.29
293(2)K
0.71073 A
o
100(2)K
Wavelength
0.71073 Ä
m
Crystal system
Space group
Unit cell dimensions
P2]/m
Pna2i
P2\/c
a = 13.203(2) Ä
b = 11.960(2) Ä
c = 7.0220(12) A
a =ß =y =90°
a = 17.333(4) A
b = 6.6392(13) Ä,
c = 19.711(4) Ä
ß = 115.01(3)°
a =15.4944(7) Ä
b = 6.3939(3) A,
c = 14.9899(7) A
ß = 105.4660(10)°
Volume
Z
Density (calculated)
Absorption coefficient
F(000)
Crystal size
6 Range for data collection
Index ranges
2055.5(7) A
6
1.364 g/cm
3
1431.27(11) A
4
1.380 g/cm
0.224 mm
632
0.2 x 0.2 x 0.4 mm
1.36 to 29.98°
-21 < h 21,
-21 < / < 2 0
16446
3
1108.8(3) Ä
4
1.314 g/cm
3
3
3
3
0.089 mm- 1
900
1
0.263 mm- 1
464
0.5 x 0.2 x 0.19 mm
3
1 . 0
x
0
. 0
1
x
0
. 0
1
mm
3
3
2.30 to 29.99°
1.14 to 22.20°
-
8
< A: < ,
8
-18 < /z < 18, -7 <
-14 < / < 20
9385
<
6
,
-1 8 < Ä < 1 8 ,-1 5 < fc < 0 ,
0 < / < 9
3363
Reflections collected
Independent reflections
Completeness
1716 [R(int) = 0.0440]
99.0%
2854 [/?(int) = 0.0818]
100.0 %
Not applied
4159 [i?(int) = 0.0301]
100.0 %
Empirical by t/»-scans
Not applied
Absorption correction
Max. and min. transmission
Refinement method
0.928 and 0.691
Full-matrix least-squares on F2
1716/1/140
0.979
Rl =0.0479, wR2 = 0.1234
Data/restraints/parameters
2854/0/353
0.972
Rl = 0.0589, wR2 = 0.1223
Rl = 0.1135, wR2 =0.1401
4159/0/266
1.057
Goodness-of-fit on F
2
Final R indices [I >2a(/)]
R indices (all data)
R l= 0.0444, wR2 =0.1199
Rl =0.0504, wR2 = 0.1237 Rl =0.1137, wR2 = 0.1558
Absolute structure parameter
Extinction coefficient
Largest diff. peak and hole
-0.1(4)
0.0007(6)
0.345 and -0.264 e •Ä
“
3
0.612 and -0.226 e • A “3
0.504 and -0.250 e - Ä " 3
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A. Orzeszko et al. • Investigation of the Thionation Reaction of Cyclic Imides
1039
Fig. 3. Molecular structure of 4a and the numbering
scheme.
ratus and were uncorrected. The FTIR spectra (in
KBr) were recorded on a Perkin-Elm er 2000 spec-
trom eter. The NM R spectra were recorded in
CDC1 using a Varian Gemini 200 MHz spectrom -
3
eter. Formal charges were calculated by means of
a semi-empirical methods (MM+ and A M I) using
the HyperChem software.
Phthalimides 3, 4 and 1: The proper anhydride
(fO mmol) was dissolved in dry DM F (20 ml).
Then fO mmol of amine (1-adamantanamine or
r-butylamine) was added. The mixture was re-
fluxed for 3 h and after cooling poured into diluted
(5% ) HCl. A fter filtration, the crude products
were crystallized from 70% EtO H .
N-(Adamant-1-yl)phthalimide (3), 2-(adamant-
l-yl)-isoindole-l,3-dione: m.p. 142-143 °C (lit.
[11]; 139 °C); yield 55%.
N-(t-Butyl)phthalimide (4), 2-ferf-butyl-isoin-
dole-l,3-dione: m.p. 64 °C (lit. [12]; 58-59 °C);
yield 59%.
Fig. 1. Independent part of the unit cell for 3. All mole-
cules have mirror plane symmetry. The scheme of num-
bering is shown for molecule A only. The unlabeled car-
bon atoms of molecule A are symmetry related to the
labeled ones.
such compounds occurs at the less-hindered car-
bonyl group giving exclusively monothioimides.
Experimental Section
General: All imides, except for 3, 4 and 7 as well
as other chemicals used were analytical grade
commercial products (Aldrich) and were used
without further purification. TLC plates silica gel
60 and silica gel 60 (200-400 mesh) were
purchased from Merck. Melting points were m ea-
sured in open capillaries on a Gallenkamp-5 appa-
N-(t-Butyl)-3,6-dichlorophthalimide (7), 2-tert-
butyl-4,7-dichloroisoindole-l,3-dione: m.p. 145-
147 °C; yield 32%; :H NM R (200 MHz, CDC13):
(3 = 7.69 (s, 2H, C
(KBr): v = 1777, 1714 cm
6
H 2), 1.57 (s, 9H, CH
(C =0).
3
); FTIR
"
1
Thionation procedure: A mixture of imide (1 -
11) (5 mmol) and Lawesson’s reagent (1.51 g,
5 mmol) in dry toluene (10 ml) was refluxed for
1 h. Then toluene was evaporated. The crude pro-
ducts were separated and purified by column flash
chrom atography using a EtOAc/hexane mixture
(
2
:1 ) for unsubstituted imides and benzene/hexane
(1:1) for others as eluent. Evaporation of the
solvents afforded the mono- and dithioimides as
orange, red, brown or yellow crystals. Analyses in-
dicated by symbols were within ±0.4% of theo-
retical values. Monocrystals of 3, 3a and 4a for X-
ray studies were obtained by crystallization from
M eOH/diethyl ether mixture. Because of very
Fig. 2. Molecular structure of 3a and the numbering
scheme.
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1040
A. Orzeszko et al. • Investigation of the Thionation Reaction of Cyclic Imides
collected using this technique. The data for struc-
ture 4a, were collected using a serial diffracto-
m eter Kuma KM-4. The full crystallographic data
small linear dimentions of monocrystals of
(0.01x0.01x1.5 mm) the data for this structure
were collected using a CCD equipment SMART-
3
A PEX at the Bruker-AXS laboratory in Karls- have been deposited with the Cambridge Crystal-
ruhe. The data for the thionation product 3a were
lographic D ata Center (CCDC-160628-16030).
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