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Hetero Analogs of Sesquifulvalene.

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Hetero Analogs of Sesquifulvalene["
By G. SeitzI*1
Heterosesquijiulvalenescontaining sulfuv or oxygen as hetero atom may be prepared, e.g.,
by condensation of cyclopentadienes with thiopyrones or pyrones in acetic anhydride.
Heterosesquijiulvalenescontaining nitrogen can be obtained from the oxygen compounds
by 0,N-exchange. The ground state of all these compounds is determined mainly by
the nonpolar resonance formula.
1. Introduction
Both the increasing pharmacological significance of
cyclopentadienylidenes [21 and the considerable interest
shown by theoretical chemists have provided impulse
to the search for new syntheses of heterosesquifulvalenes 131. These compounds are formally derived
from sesquifulvalene (I) 141, replacement of a
-CH= CH- group of the carbocyclic seven-membered
ring by a hetero atom such as oxygen [5,4CI, sulfur [5,4c],
or nitrogen 161, giving cyclopentadienylidenepyrans,
-thiopyrans, and -1,4-dihydropyridines, respectively.
Compound ( I ) and its hetero analogs (2) are characterized by cyclic cross-conjugated x-bond systems,
which can be described to a first approximation by a
covalent resonance structure and a dipolar one.
If the dipolar form were to make a large contribution
to the resonance hybrid, a situation that would be
favored by the gain in resonance energy of two aromatic 6x systems, then stable molecules having high
dipole moments would result and the bond order of
the intercyclic C=C double bond would be reduced.
Such predictions 171, based on simple HMO calculations, prove inapplicable [4a] to sesquifulvalene, which
is in fact a highly unstable compound whose properties resemble more those of a reactive polyolefin. In
contrast, the nitrogen-containing heterosesquifulvalenes (2), having X = N-R [61, are relatively stable.
With this in mind, our interest became focused on the
chemical behavior of the oxygen and sulfur analogs.
The present article reports on a simple method of
synthesis and a number of chemical and physical
properties of these heterosesquifulvalenes.
2. Synthesis of Heterosesquifulvalenes
containing Oxygen and Sulfur as Hetero Atoms
(2)
X = 0, S , N-R
[*I
Doz. Dr. G. Seitz
Institut fur Pharmazeutische Chemie und
Lebensmittelchemie der Universitat
355 Marburg, Marbacher Weg 6 (Germany)
[I] From the Habilitation Thesis by G. Seitz, Universitat Marburg 1968, also Part 4 of Cyclopentadienylidenes. - Part 3:
Tetrahedron Letters 1968, 2305.
[2] C. T. Bahner, H. Kinder, D . Brotherton, J. Spiggle, and L .
Gutmann, J. med. Chem. 8, 390 (1965); P . W. Thies, Dtsch. Apotheker-Ztg. 107, 1411 (1967).
[3] For recent reviews see D. Lloyd: Carbocyclic Non-Benzenoid
Aromatic Compounds. Elsevier, Amsterdam 1966; E. D . Bergmann, Chem. Reviews 68, 41 (1968).
141 a) H. Prinzbach, Angew. Chem. 73,169 (1961); H. Prinzbach,
D . Seip, L . Knothe, and W. Faisst, Liebigs Ann. Chem. 698, 34
(1966); b) Y. Kitahara, I. Murata, and S . Katagiri, Angew. Chem.
77, 345 (1965); Angew. Chem. internat. Edit. 4 , 353 (1965);
c) G. Seitz, Angew. Chem. 79, 96 (1967); Angew. Chem. internat.
Edit. 6, 82 (1967); d) E . Koerner v. Gustorf, M . C. Henry, and P .
V. Kennedy, Angew. Chem. 79, 616 (1967); Angew. Chem. internat. Edit. 6, 627 (1967).
[ 5 ] D . Lloyd and F. J. Wasson, Chem. and Ind. 1963, 1559;
J. chem. SOC.(London) C 1966, 1086.
161 a) F. KrBhnke, K . Ellegast, and E. Bertram, Liebigs Ann.
Chem. 600, 176 (1956); D . N. Kursanov, N. K . Baranetskaja, and
V. N . Setkina, Proc. Acad. Sci. USSR, Chem. Sect. (English
translation) 113, 191 (1957); J . A. Berson, E. M . Evleth, and 2.
Hamlet, J. Amer. chem. SOC.87, 2887 (1965); b) G. V. Boyd and
L. M . Jackman, J. chem. SOC.(London) 1963, 548.
478
Two methods for the preparation of cyclopentadienylidenepyrans and -thiopyrans have hitherto become
known. The first method is restricted to phenyl-substituted cyclopentadienes and is based on the reaction
of diazocyclopentadienes ( 3 ) with 4-thiopyrones (4)
in xylene at elevated temperatures to give ( 5 ) 151.
The second synthetic route utilizes the finding that
substituents exhibiting a -M or -I effect increase the
A -
c
6
H
xb
sH5
C6H5
HSC
X
CH,
6,
(3)
(4)
(5)
x=o,s
[7] J . D. Roberts, A. Streitwieser, and C. M . Regan, J. Amer.
chem. SOC.74, 4579 (1952).
Angew. Chem. internat. Edit.
Vol. 8 (1969)1 No. 7
reactivity of the cyclopentadienes ( 6 ) and promote
their condensation with ketones such as (7), X = O,S,
or -CH=CH-,in acetic anhydride[4c,11. A number
of heterosesquifulvalenes (8aj -(8e) that have been
are listed in
prepared by the “anhydride method”
Table 1.
Provided that the indene system (12) carries electronattracting substituents, the anhydride method can
also be used for the synthesis of the hetero analogs of
9,l O-benzosesquifulvalenes[101,indenylidenepyrans and
-thiopyrans (13), X = O,S[9].
ah2
0
+
H3C
X
-
(12a). R’ = COZCH3, R2 = H
CH3
(12b), R’ = R2 = CO,C,Hs
H rR3Z R
R2 ‘
E
l
R4
@
I 1
H3
X
X
CH,
CH3
(13)
Table I.
Cyclopentadienylidenepyrans and -thiopyrans prepared by
the “anhydride method”.
R’
RZ
R3
R4
C02CH3
CI
COzCHi
CI
COzCH,
COzCH,
CI
CO2CH3
CN
H
CN
COLCHJ H
H
H
CN
H
CI
H
H
0
0
227
>1so
(de-
The success of these experiments provided some justification
for the expectation that, like the heterocyclic ketones, the isox-electronic system tropone (14) should also condense with
activated cyclopentadienes in acetic anhydride. Indeed, both
52
45
S
0
camp.)
171
>260
S
(decamp.)
168
19
12
25
Even those cyclopentadienes formed by retro-DielsAlder reaction at elevated temperatures are activated
sufficiently by only one such substituent, and can
consequently be intercepted in the equilibrium (9) +
(10) by pyrone or thiopyrone. The resulting monosubstituted heterosesquifulvalenes ( l l a ) and ( I l b ) are
also stable compounds; the major product ( I l b j can
be separated from the minor component of the isomeric mixture by adsorption chromatography on
silica gel.
tropone and benzotropone could be converted extremely
smoothly into the sesquifulvalenes (16) and (1 7) by treatment
with tetramethyl cyclopentadienetetracarboxylate[ill (15).
(Ilbl
(Ilul
I81 Regarding condensation reactions of other CH acids with
4-pyrones, cf. L. L. Woods, J. Amer. chem. SOC.80, 1440 (1958);
F. Eiden, Angew. Chem. 71, 747 (1959); Arch. Pharmaz. 293, 404
(1960); M . Ohtu and H . Kato, Bull. chem. SOC. Jauan 32, 707
(1959); J . Kelemen and R. Wizinger, Helv. chim. Acta 45, 1908
(1962).
Angew. Chem. internat. Edit. Vof. 8 (1969)
No. 7
[91
.~G . Seitz, Arch. Pharmaz. 300, 1016 (1967).
.
.
[lo] H. Prinzbach, D . Seip, and G. Englerr, Liebigs Ann. Chem.
6983 57 (1966).
[I 11 G. Seifz, Angew. Chem. 78,680 (1966); Angew. Chem. Internat. Edit. 5, 670 (1966).
479
An analogous synthesis of the tetrachloro derivative ( I 6),
C1 instead of C02CH3, has also been reported [121.
The synthesis of substituted heterosesquifulvalenes and
a number of hetero analogs of 9,10-benzosesquifulvalene, as well as the condensation of tropone and
benzotropone, illustrate the scope of the anhydride
method. The limitations of this synthetic technique
become apparent when one considers the unsuccessful
attempts to condense unsubstituted cyclopentadiene,
indene, or fluorene with pyrones.
3. Reactivity of Heterosesquifulvalenes
A highly polar ground state of the heterosesquifulvalenes, in line with the dipolar formula ( I s ) , would
suggest amphoteric character and therefore permit
electrophilic reactions in the five-membered ring and
nucleophilic reactions in the six-membered ring.
(8a), the analog having X = S, and (16) are all protonated in a uniform manner, though at the ester
carbonyl group; NMR and electronic spectra suggest
the structures (20aj, (20b), and (ZOc), having a symmetrical hydrogen bond @I.
3.2. Electrophilic Substitution
Electrophilic substitutions occur in good yields, even
at room temperature. Friedel-Crafts acylation of (23)
with acetyl chloride/SnC14 affords the monoacetylated
compound (22). An excess of bromine converts (23)
into the dibromo derivative (21), whereas reaction
with p-nitrobenzenediazonium fluoroborate probably
yields the phenylhydrazone (25), which is tautomeric
with (24).
Both such reactions do take place, as shown in the
following examples.
H3C
t
NH3
0
f
3.1. Electrophilic Addition
Heterosesquifulvalenesare relatively strong "z bases".
For instance, in strong acids, such as perchloric acid
or trifluoroacetic acid, (86) undergoes regiospecific
CF,COOH
___)
H3C @CH3
OC H3
1191
(86)
C02CH3
quantitative C-protonation to give (19) [1,4%5,6b, 131; CH302C
the structure of the product is proved by NMR and
UV spectra.
'
"
~
0
~
0
~
7
-
(24) H3C
CH30-CqC-OCH3
CH302C
/
CH30-C,
C02CH3
-A
k-OCH3
3.3. Nucleophilic Reactions
C H ~ O z C ~ C O z C H 3
@
(ZOa), X = 0
(ZOb), X = S
(ZOC),
X = -CH=CH-
-[12] E. D. Bergmann, Chem. Reviews 68, I4 (1968).
[I31 E. D. Bergmann and I. Agranat,Tetrahedron 22,1275 (1966).
480
Pyrones and pyranylidene compounds are known to be
readily convertible into pyridine derivatives by treatment with primary amines [5,*4J. By analogy, replacement of oxygen in cyclopentadienylidenepyrans
should also be feasible. Indeed, heterosesquifulvalenes
containing oxygen as hetero atom react almost quantitatively, irrespective of substituents, with aliphatic
amines to give the aza analogs (26). This nucleophilic
Angew. Chem. internat. Edit. 1 Vol. 8 (1969)1 NO.7
substitution proves a useful addition to the known
syntheses of unsubstituted or annelated nitrogen
analogs of sesquifulvalene.
R3
f8)
+
R2
The heterosesquifulvalenes (23), (27), and (28),
whose five-membered rings are substituted in two
positions, are suitable for determination of the free
energy of activation AG,+for rotation around the intercyclic bond. (Figure 1 reproduces sections of the
relevant NMR spectra measured at 40 "C.)
R4
R-NHz
t
)
x=o
I
I
I
80
70
60
4. Polarity and Electron Distribution
I
70
6.0
5.0
7.0
-6lppml
6.0
5.0
8.0
NMR data provide no unequivocal information
regarding the shielding of the protons attached to the
five- and six-membered rings of heterosesquifulvalenes;
the anisotropic effects of the substituents do not permit
direct relationships to be observed between the chemical shifts and the .n-electron density distribution. On
the other hand, solvatochromism effects [I51 should at
least furnish qualitative information about the polarity
of the ground state. All the heterosesquifulvalenes
having oxygen or sulfur as hetero atom that have been
isolated so far show, to a greater or lesser extent, a
pronounced positive solvatochromism. The ground
state is therefore determined primarily by the nonpolar resonance formula. However, measurements of
dipole moments and determination of the free energy
of activation AG,+ for rotation around the central
C-C doubIe bond suggest that the dipolar form also
contributes to the resonance hybrid.
Compound (23) has a dipole moment of 5.1 D (20 OC,
benzene), a finding that becomes all the more remarkable when one considers that the sense of the 0 moment (disregarding the effect of the two ester groups,
which is not readily estimable) is opposed to that of the
x moment [161.
I
8.0
Fig. 1. Partial NMR spectra (60 MHz) of (23), (27). and (28). The
signals due to the pyran protons are indicated by arrows.
In addition, A G was
~ also determined for the acylated
product (22) and (8e). The different rates of rotation
around the central bond can be calculated from the
signals of the pyran protons (shown by arrows). The
shapes and positions of the peaks are temperature
dependent (Figure 2).
The relevant AGZ values could be calculated from the
temperature of coalescence T, and the maximum
COzCHj
(23j,
x=0
(27).
. .. X = S
(28). X = N-C4Hg
[141 K. Dimroth, Angew. Chem. 72, 331 (1960), and further
literature cited there; F. Eiden, Naturwissenschaften 47, 60
(1960); Arch. Pharmaz. 295, 607 (1962).
[151 For recent reviews see p. 336 in H. A. Staab: Einfuhrung in
die theoretische organische Chemie, 1 s t Edit., Verlag Chemie,
WeinheimIBergstr. 1959; C. Reichardt, Angew. Chem. 77, 30
(1965); Angew. Chem. internat. Edit. 4,29 (1965).
[161 Cf. A. Streitwieser: Molecular Orbital Theory. J . W i k y ,
New York 1962, p. 139ff.
Angew. Chem. internat. Edit. J Vol. 8 (1969) No. 7
t
7.0
8.0
-6
lpprni
Fig. 2. Temperature dependence of the peaks due to the pyran protons
(shown by arrows) in (23).
48 1
Cpd.
Av (Hz)
(22)
(23)
(27)
(8e)
47
73
48
52
I
Tc (OK)
279
339
280
384
I
AG$ (kcal/mole)
X
13.7
16.5
13.8
19.0
0
0
S
S
(29), X = N-C,H,
(30), X = 0
5. Conclusion and Outlook
Within certain limits the anhydride method has proved
a simple and effective process for the preparation of
substituted sesquifulvalenes and of the iso-z-electronic
cyclopentadienylidenepyrans and -thiopyrans. Only a
selection of the possible reactions has been described
in this article. Preliminary experiments have shown
that various other ketones that are iso-rc-electronic
with tropone and contain more than one hetero atom
also undergo condensation to heterosesquifulvalenes
by the same synthetic route. Similarly, the benzotropone analogs furo[3,4-d]tropone and thieno[3,4-d]tropone can also be converted into heterosesquifulvalenes that may be considered as vinylogs of the
cyclopentadienylidenepyrans and -thiopyrans, respectively.
1171 Regarding method of calculation cf. J . A . Pople, W. G.
Schneider, and H. J . Bernstein: High Resolution Nuclear Magnetic Resonanz. McGraw-Hill, New York 1959, p. 223; S. Glasstone, K . J . Laidler, and H. Eyring: The Theory of Rate Processes.
McGraw-Hill, New York 1941, p. 194.
I181 G. Seitz, unpublished experiments.
The author wishes to thank the Deutsche Forschungsgemeinschaft for their support of his investigations
described in this article.
Received: October 4, 1968
[A 704 IEI
German version: Angew. Chem. 81,518 (1969)
Thiiranium Ions as Reaction Intermediates
By Wolfgang H. Mueller[*]
The addition of sulfenyl chlorides or suvur dichloride to unsaturated compounds proceeds
via thiiranium ions. The present article reviews the electronic and steric factors influencing
the nature oj these ions and their effectson subsequent ring opening and product formation.
For the purpose of this discussion results primarily from electrophilic ring opening have
been chosen to illustrate these factors. Solvent and temperature efects have been disregarded.
1. Introduction
Thiiranium ions (episulfonium ions) as chemical intermediates were first proposed during studies of the
neighboring group effect of sulfur in extremely reactive
[*I Dr. Wolfgang H. Mueller
Central Basic Research Laboratory
Esso Research and Engineering Co.
Linden, N.J. 07036 (USA)
482
P-haloalkyl thioethers of the “mustard gas” type,
S(CH2CH2C1)2[I ,zJ. For instance, the intervention of
a thiiranium ion (2) was postulated to account for
a single product (4) obtained on chlorination of the
isomeric alcohols ( I ) and (3).
[l] R . C. Fuson, C . C. Price, and D . M . Burness, J. org. Chemistry 11, 475 (1946).
[2] P. D . Bartlett and C. G . Swain, J. Amer. chem. SOC.71, 1406
(I 949).
Angew. Chem. internat. Edit. f Vol. 8 (1969) 1 No. 7
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