Chiroptical Spectra of 1,2-Cyclopropanedicarboxylic Monothioimides

Full text of DOI:10.1021/jo961724p

1860
J . Org. Chem. 1997, 62, 1860-1862
Ta ble 1. Electr on ic Absor p tion (UV-vis) a n d Cir cu la r
Dich r oism (CD) Da ta of Com p ou n d s 1-5
Ch ir op tica l Sp ectr a of
1,2-Cyclop r op a n ed ica r boxylic
Mon oth ioim id es1
compd
solva
UV λ, nm (ꢀ)
CD λ, nm ([θ] × 10-3
)
1
C
M
C
M
C
M
C
M
C
M
C
408 (46)
400 (38)b
414 (33)
405 (33)
414 (44)
406sh (39)b
418 (42)
c
412 (56)
c
425 (35)
414 (32)
415 (12.7)
410 (9.2)
418 (11.7)
412 (9.7)
413 (12.5)
410 (9.3)
414 (12.3)
413 (10.2)
414 (12.6)
409 (10.3)
Maria J . Milewska, Maria Gdaniec,† and
Tadeusz Połon´ski*
2
3
Department of Chemistry, Technical University of Gdan˜sk,
80-952 Gdan´sk, Poland, and Faculty of Chemistry,
A. Mickiewicz University, 60-780 Poznan´, Poland
4a
4b
5
Received September 9, 1996
434 (1.39), 383 (-0.04)
460 (0.02), 405 (-0.73)
398 (-0.76)e
M
The structure, electronic absorption spectra, and chi-
roptical properties of imides have been a subject of
considerable interest in recent years.2,3 These compounds
show two weak n-π* absorption bands followed by a
moderately intense π-π* transition in the region of 270-
200 nm as predicted by semiempirical MO calculations.2a,c
It is well known that the substitution of sulfur for oxygen
in the carbonyl group shifts absorption maxima to much
longer wavelengths.4 This allows observation of the
lowest energy excited states of thiocarbonyls at the visible
or near-UV region. There are some reports on the
electronic and circular dichroism (CD) spectra of dithio-
imides,5,6 but much less is known on the spectroscopic
properties of monothioimides.6
In this paper, we describe the electronic and chiroptical
spectra of cis-1,2-cyclopropanedicarboxylic monothioim-
ides 1-4. Their bicyclic skeleton is relatively rigid due
to steric constraints imposed by the cyclopropane ring,
and thus, the influence of conformational effects on the
CD spectra should be negligible. By analogy with the
parent imides, the geometries of which are known from
the X-ray structures,3,7 the 3-azabicyclo[3.1.0]hexane
moiety in 1-4 is expected to adopt a sofa-like (half-boat)
conformation with the â-carbon atom being out of the
plane formed by the remaining ring atoms. For com-
parison, we prepared and measured the CD of the related
monocyclic thioimide 5, for which much more conforma-
tional freedom was expected. Its geometry in the solid
state was established by X-ray crystallography.
KBrd
M ) methanol, C ) cyclohexane. Shoulder. c No observable
a
b
maximum of absorption. KBr pellet. e The approximate value
d
determined from a w/w concentration using a KBr density of 2.75
g cm-3
.
Resu lts a n d Discu ssion
The synthesis of the compound 1 with chirality solely
due to the sulfur substitution has been described earlier.8
Thioimides 2-5 were obtained by thionation of corre-
sponding imides of the known absolute configuration3
with Lawesson’s reagent.9 Owing to a steric effect of the
R-substituent, the reaction occurs at the less hindered
carbonyl to give single isomers 3-5. Only in the case of
2 was the reaction product contaminated with a small
amount of the second isomer and purified by fractional
crystallization. Small quantities of the corresponding
dithioimides formed during the thionation can be readily
separated by column chromatography in the workup
procedure.
The UV-vis spectrum of the thioimide 1 in cyclohexane
contains two weak absorption bands appearing as a
maximum at 408 nm (ꢀ 46) and a shoulder at 326 nm
(97), in addition to a strong absorption at 274 nm
(18 000), shifting in methanol to 400, 320, and 276 nm,
respectively. In the six-membered ring compound 5 the
analogous UV bands are shifted to slightly longer wave-
lengths (Table 1). A similar observation concerning the
electronic spectra of thiosuccinimide and thioglutarimide
has been described by Berg and Sandstro¨m.6 The inten-
sity of the observed absorptions and the solvent effects
suggest the n-π* character of two lowest energy transi-
tions and the π-π* nature of the strong absorption at
the shorter wavelengths. The shape of the molecular
orbitals involved in these transitions was established by
the CNDO/S-CI10 calculations for 1. According to this
method, the major components of the initial n orbitals,
for the first and the second n-π* excitations, are the
sulfur 3p and oxygen 2p functions, respectively, whereas
the lowest energy π* orbital is delocalized over both
thioimide and cyclopropane moieties. Thus, the thioim-
ide group can be considered as “conjugated” with the
three-membered ring,11 and together they form an inher-
ently chiral (dissymmetric) chromophore.
R
Ph
O
O
S
N
S
N
R1
Me
1, R = R1 = H
5
2, R = Me, R1 = H
3, R = Pri, R1 = H
4a, R = Ph, R1 = H
4b, R = Ph, R1 = Me
† A. Mickiewicz University.
(1) Presented in part at the XIth European Symposium of Organic
Chemistry, Warsaw, J une 1995.
(2) (a) Połon´ski, T. J . Chem. Soc., Perkin Trans. 1 1988, 629 and
639. (b) Połon˜ski, T.; Milewska, M. J .; Gdaniec, M.; Gilski, M. J . Org.
Chem. 1993, 58, 3134. (c) Xu, S.; Clark, L. B. J . Am. Chem. Soc. 1994,
116, 9227.
(3) Połon´ski, T.; Milewska, M. J .; Katrusiak, A. J . Org. Chem. 1993,
58, 3411.
(4) Maciejewski, A.; Steer, R. P. Chem. Rev. 1993, 93, 67.
(5) (a) Połon´ski, T. J . Chem. Soc., Chem. Commun. 1988, 854. (b)
Fa¨lth, L.; Hakansson, U.; Sandstro¨m, J . THEOCHEM 1989, 186, 239.
(c) Meskers, S. C. J .; Połon´ski, T.; Dekkers, H. P. J . M. J . Phys. Chem.
1995, 99, 1134.
(8) Milewska, M. J .; Połon´ski, T. Tetrahedron: Asymmetry 1994, 5,
359.
(9) (a) Pedersen, B. S.; Scheibye, S.; Nilsson, N. H.; Lawesson, S.-
O. Bull. Soc. Chim. Belg. 1978, 87, 223. (b) Yde, B.; Yousif, N. M.;
Pedersen, U.; Thomsen, J .; Lawesson, S.-O. Tetrahedron 1984, 40,
2047. (c) For a review see: Cava, M. P.; Levinson, M. J . Tetrahedron
1985, 41, 5061.
(6) Berg, U.; Sandstro¨m, J . Acta Chem. Scand. 1966, 20, 689.
(7) Epstein, J . W.; Brabander, H. J .; Fanshave, W. J .; Hofmann, C.
M.; McKenzie, T. C.; Safir, S. R.; Osterberg, A. C.; Cosulich, D. B.;
Lovell, F. M. J . Med. Chem. 1981, 24, 481.
(10) Pople, J . A.; Beveridge, D. Approximate MO Theory; McGraw
Hill: New York, 1970; Chapter 3.5.
(11) J orgensen, W. L.; Salem, L. The Organic Chemist’s Book of
Orbitals; Academic Press: New York, 1973.
S0022-3263(96)01724-0 CCC: $14.00 © 1997 American Chemical Society

Notes
J . Org. Chem., Vol. 62, No. 6, 1997 1861
Ch a r t 1
The CD spectra of the bicyclic thioimides 1-4 are
characterized by a strong positive Cotton effect (CE),
about 415 nm corresponding to the long-wavelength n-π*
transition. A relatively high value of the dissymmetry
factor (g ) ∆ꢀ/ꢀ of 0.08) indicates magnetic character of
this transition.12 In contrast to the parent imides3 and
related dithioimides,13 the CE magnitude remains almost
unaffected by substituents and is only weakly influenced
by solvent changes. Moreover, both imides and dithio-
imides show a CD considerably weaker than those of 1-4.
Apparently, the inherent chirality of the chromophore
(chiral first sphere according to Snatzke doctrine of
spheres)14 is responsible for the strong CEs of the title
compounds, and its contribution to the CE outweighs that
made by the ring substituents (chiral third sphere).
Thus, the CE sign associated with the first n-π* excita-
tion is determined by the helicity of the chromophore
(Chart 1). The above situation closely resembles that
encountered in cyclopropyl ketones, where the “conjuga-
tion” of the carbonyl group with the three-membered ring
results in strong CEs.15 There are also some analogies
with the 1,2-cyclopropanedicarboximides, however, in
that case contribution from the cyclopropane moiety to
the CE may arise only upon distortion of the imide
chromophore from the Cs symmetry, i.e., deviation of the
imide group from planarity induced by substituents or
solvation effects.3
F igu r e 1. CD and UV spectra of 4b in cyclohexane (s) and
CD of 5 in cyclohexane (---) and methanol (-‚-).
The CD curves of the monocyclic compound 5 are
strikingly different (Figure 1). They exhibit bisignate
CEs within the first n-π* band; their magnitudes are
much weaker than that of the related thioimide 4b, and
moreover, they are extremely sensitive to solvent changes.
There are two reasons for a relatively low intensity of
the overlapping CEs: the symmetric character of the
chromophore “restricted” to the thioimide group, which
gains optical activity only from the perturbation caused
by chiral environment and a conformational flexibility
of the six-membered ring in 5. This compound may adopt
two possible sofa conformers: one with the equatorial and
the second with the axial phenyl substituent, contribut-
ing with the opposite signs to the CE. A conformational
equillibrium between these forms can rationalize the
bisignate CD curve with low CE magnitudes. The
semiempirical AM1 calculations16 revealed nearly the
same heats of formation for both conformers, and thus,
their populations in solution may not differ significantly.
The X-ray structure of 517 (Figure 2) shows that the
equatorial conformer is preferred in the crystal state. The
F igu r e 2. X-ray structure of thioimide 5.
CD spectrum measured in the solid state (KBr pellet)
exhibits the negative and monosignate CE in the n-π*
region, and therefore, the negative CE should be associ-
ated with equatorial conformer and the positive one
probably with the axial form. According to the solution
spectra the first one dominates in polar media and the
second one in hydrocarbon solvents. In this case, as well
as in the case of other monothioglutarimides, the ring
chirality (chiral second sphere) is expected to play an
important role in determination of the CE sign. How-
ever, predictions based solely on the ring geometry might
be risky for these compounds since other factors like
inherent chirality of the chromophore and vicinal effects
of substituents may also contribute to the CE; e.g., the
(12) Mason, S. F. Molecular Optical Activity and the Chiral Dis-
criminations; Cambridge University Press: Cambridge, 1982; p 48.
(13) Połon´ski, T. unpublished results.
(14) Snatzke, G. Angew Chem., Int. Ed. Engl. 1979, 18, 363.
J orgensen, W. L.; Salem, L. The Organic Chemists Book of Orbitals;
Academic Press: New York, 1973.
(15) (a) Djerassi, C,; Klyne, W.; Norin, T.; Ohloff, G.; Klein, E.
Tetrahedron 1965, 21, 163. (b) Lightner, D. A.; Beavers, W. A. J . Am.
Chem. Soc. 1971, 93, 2677. (c) Lightner, D. A.; J ackman, D. E.
Tetrahedron Lett. 1975, 3051.
(16) Dewar, M. J . S.; Zoebisch, E. G.; Healy, E. F. Stewart, J . J . P.
J . Am. Chem. Soc. 1985, 107, 3902.
(17) The authors have deposited experimental details concerning
the crystal structure determination of 5, atomic coordinates, anisotropic
displacement parameters of non-H atoms, and lists of bond lengths
and angles with the Cambridge Crystallographic Data Centre. The
coordinates can be obtained, on request, from the Director, the
Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge
CB2 1EZ, UK.

1862 J . Org. Chem., Vol. 62, No. 6, 1997
Notes
Anal. Calcd for C11H9NOS (203): C, 65.02; H, 4.46; N, 6.89;
S, 15.76. Found: C, 65.05; H, 4.15, N, 6.72; S, 15.73.
crystal structure of 5 exhibited slight deviation of the
thioimide group from planarity reflected by the C-N-
C)S and C-N-C)O torsional angles [174.3(3)° and
-175.7(4)°, respectively].
Surprisingly, the compounds 1-5 do not show measur-
able CEs corresponding to the second n-π* transition,
probably due to the overlap with much stronger π-π*
band. The CE associated with the π-π* absorption
exhibits sign opposite to that observed for the long-
wavelength n-π* excitation; e.g., 1 shows [θ] -65 000
at 280 nm in cyclohexane. However, measurements in
this region are less reliable due to the low dissymmetic
factor (g of 0.001) for the electric dipole allowed π-π*
transition.
(1S,5R)-3-Meth yl-1-p h en yl-4-th ioxo-3-a za bicyclo[3.1,0]-
h exa n -2-on e (4b ) was obtained from (1S,2R)-N-methyl-1-
phenyl-1,2-cyclopropanedicarboximide3 in a manner similar to
that for compound 2: mp 136-137 °C (from heptane); [R]20D +45
(c 1, C6H6); [R]20546 +107 (c 1, C6H6); IR (KBr) ν 1730, 1355, 1175,
1
1020 cm-1; H NMR (CDCl3) δ 7.38 (m, 5 H), 3.35 (dd, J ) 3.5,
8.0 Hz, 1 H), 3.23 (s, 3 H), 1.97 (dd, J ) 4.6, 8.0 Hz, 1 H), 1.86
(dd, J ) 3.5 and 4.6 Hz, 1 H); 13C NMR (CDCl3) δ 207.9, 176.4,
132.1, 128.8, 128.7, 128.3, 37.4, 37.1, 31.3, 28.6; UV (cyclohexane)
λmax 412 (ꢀ 56), 332 (82), 280 nm (19 800).
Anal. Calcd for C12H11NOS (217): C, 66.35; H, 5.10; N, 6.45;
S, 14.72. Found: C, 66.38; H, 4.90; N, 6.38; S, 14.44.
(S)-N-Meth yl-2-p h en ylglu ta r im id e. (S)-2-Phenylglutaric
acid18 (1.0 g, 5 mmol) was refluxed with acetyl chloride (5 mL)
for 20 min and evaporated to dryness. The residue was treated
with a 30% ethanolic solution of methylamine (3 mL) with
cooling of the reaction mixture in an ice bath. After evaporation
of the solvent, 5% hydrochloric acid (5 mL) was added, and the
solution was extracted with chloroform. The organic layer was
dried (MgSO4), the solvent was evaporated, and the result
N-methylamide was refluxed with acetyl chloride (5 mL) for 30
min. After evaporation to dryness, the title product was
crystallized from toluene: yield 0.62 g (60%); mp 129-130 °C;
[R]22546 -10.7 (c 2.6, CHCl3); 1H NMR (CDCl3) δ 7.4-7.2 (complex
m, 5 H), 3.84 (dd, J ) 5.5 and 9.0 Hz, 1 H), 3.23 (s, 3 H), 2.73
(m, 2 H), 2.22 (m, 2 H); 13C NMR (CDCl3) δ 173.4, 172.4, 138.0,
128.8, 127.9, 127.5, 48.5, 31.3, 26.8, 25.2.
Exp er im en ta l Section
All spectroscopic measurements were carried out as described
previously.2b The synthesis of compound 1 has been published
elsewhere.8
(1S,5R)-1-Met h yl-4-t h ioxo-3-a za b icyclo[3.1.0]h exa n -2-
on e (2). A mixture of (1S,2R)-1-methyl-1,2-cyclopropanedicar-
boximide3 (0.345 g, 3 mmol) and Lawesson’s reagent (0.606 g,
1.5 mmol) was refluxed in benzene (15 mL) for 1 h. The reaction
mixture was chromatographed on silica gel with chloroform as
eluent. A small orange-red fraction of the dithioimide was
collected first followed by a yellow fraction of the title product.
After evaporation of the solvent the residue (0.21 g) was
crystallized from toluene-hexane: yield 0.105 g (26%); mp 69
°C; [R]22D +166 (c 0.44, C6H6); IR (KBr) ν 1725, 1450, 1210, 1175
cm-1; 1H NMR (CDCl3) δ 8.73 (br s, 1 H), 2.84 (ddd, J ) 1.8, 3.2,
8.0 Hz, 1 H), 1.68 (dd, J ) 3.2, 4.6 Hz, 1 H), 1.53 (dd, J ) 4.6,
8.0 Hz, 1 H), 1.48 (s, 3 H); 13C NMR (CDCl3) δ 209.3, 178.8, 37.8,
30.7, 12.8; UV (cyclohexane) λmax 414 (ꢀ 33), 273 nm (16 400).
Anal. Calcd for C6H7NOS (141): C, 51.04; H, 5.00; N, 9.92;
S, 22.71. Found: C, 51.12; H, 4.91; N, 9.88; S, 22.82.
Anal. Calcd for C12H13NO2 (203): C, 70.92; H, 6.45; N, 6.89.
Found: C, 70.85; H, 6.31; N, 7.00.
(S)-1-Meth yl-3-p h en yl-6-th ioxo-2-p ip er id in on e (5) was
obtained from the above imide in a manner similar to that for
compound 2: mp 84-85 °C (toluene-heptane); [R]20D +109 (1.9,
C6H6); IR (KBr) ν 1695, 1360, 1275, 1120 cm-1; 1H NMR (CDCl3)
δ 7.4-7-2 (complex m, 5 H), 3.94 (t, J ) 7.5, Hz, 1 H), 3.67 (s,
3 H), 3.42 (dt, J ) 7.0 and 18.1 Hz, 1 H), 2.24 (m, 2 H); 13C
NMR (CDCl3) δ 209.1, 171.0, 138.0, 128.8, 127.9, 127.6, 127.4,
127.2, 49.2, 42.1, 34.2, 26.8.
Anal. Calcd for C12H13NOS (219): C, 65.72; H, 5.97; N, 6.39;
S, 14.62. Found: C, 65.67; H, 5.84; N, 6.35; S, 14.57.
X-r a y Diffr a ction An a lysis. Crystal structure analysis was
carried out for the racemic thioimide 5.
Crystal data for C12H13NOS (5): orthorhombic, space group
Pbca, a ) 16.721(8) Å, b ) 6.343(4) Å, c ) 22.012(8) Å, V )
2335(1) Å3, Z ) 8, Dcalcd ) 1.248 g cm-3, λ(Mo KR) ) 0.710 73 A,
T ) 292 K, R1 ) 0.044, wR2 ) 0.109 for 1842 independent
reflections with I > 2σ(I).
(1R,5R)-1-Isop r op yl-4-t h ioxo-3-a za b icyclo[3.1.0]h exa n -
2-on e (3) was obtained from (1R,2R)-1-isopropyl-1,2-cyclopro-
panedicarboximide3 in a manner similar to that for compound
2: mp 84 °C (from hexane); [R]20 +147.5 (c 2, C6H6); IR (CCl4)
D
ν 3415, 1755, 1430, 1150, 1025 cm-1
;
1H NMR (CDCl3) δ 9.16
(br s, 1 H), 2.81 (ddd, J ) 1.8, 4.0, 7.4 Hz, 1 H), 2.12 (sep, J )
6.9 Hz, 1 H), 1.57 (m, 2 H), 1.04 (d, J ) 6.9 Hz, 3 H), 0.98 (d, J
) 6.9 Hz, 3 H); 13C NMR (CDCl3) δ 209.6, 178.5, 40.7, 35.3, 27.7,
26.1, 19.6, 18.9; UV (cyclohexane) λmax 414 (ꢀ 44), 275 nm
(13 200).
Anal. Calcd for C8H11NOS (169): C, 56.80; H, 6.55; N, 8.28;
S, 18.93. Found: C, 56.75; H, 6.77; N, 8.44; S, 18.73.
(1S,5R)-1-P h en yl-4-t h ioxo-3-a za b icyclo[3.1.0]h exa n -2-
on e (4a ) was obtained from (1S,2R)-1-phenyl-1,2-cyclopro-
panedicarboximide3 in a manner similar to that for compound
Ack n ow led gm en t. This work was supported in part
by the Committee of Scientific Research.
2: mp 115-116 °C; [R]21 +139 (c 1, C6H6); IR (CCl 4) ν 3410,
D
J O961724P
1760, 1430, 1150, 1020 cm-1
;
1H NMR (CDCl3) δ 8.76 (br s, 1
H), 7.26 (s, 5 H), 3.28 (m, 1 H), 2.02 (m, 2 H); 13C NMR (CDCl3)
δ 208.0, 176.9, 131.5, 128.8, 128.7, 128.4, 39.1, 38.5, 30.5; UV
(cyclohexane) λmax 418 (ꢀ 60), 332 (136), 277 nm (19 700).
(18) (a) Westman, L. Ark. Kemi 1958, 11, 431. (b) Kawazu, K.; Fujita,
T.; Mitsui, T. J . Am. Chem. Soc. 1959, 81, 932.