1,3-Dipolar cycloadditions, 116. The formation of 1,3-dithiolanes from aromatic thioketones and diazomethane - The mechanism of the Schonberg Reaction

Article abstract of DOI:10.1002/(sici)1099-0690(200005)2000:9<1685::aid-ejoc1685>3.0.co;2-6

Reactions of diaryl thioketones with diazomethane at room temperature afford 4,4,5,5-tetraaryl-1,3-dithiolanes; the scope of this surprising 2:1 interaction has been studied for decades (Schonberg Reaction). The clue to the mechanism was our observation that the stoichiometry is 1:1 at -78 °C, and 2,5-dihydro-2,2-diaryl-1,3,4-thiadiazoles are formed as primary [2+3] cycloadducts. They lose N₂ at -45 °C in first-order reactions generating diaryl thioketone S-methylides which can be intercepted by thioketones (→1,3-dithiolanes), multiple CC bonds, or acids HX. In the absence of trapping reagents, the elusive intermediates either dimerize furnishing 2,2,3,3-tetraaryl-1,4-dithianes or give rise to 2,2-diaryl-thiiranes by electrocyclization. Beyond thiobenzophenone and diazomethane, our main model reaction, the studies involve fluorene-9-thione, 4,4-dimethoxy- and 4,4- dichloro-thiobenzophenone. The ring of 2,5-dihydro-2,2-diphenyl-1,3,4- thiadiazole (8) is opened by LDA at -78 °C and derivatives of anion 12 are obtained. - In summa: The Schonberg reaction consists of two 1,3-dipolar cycloadditions, linked by a 1,3-dipolar cycloreversion.

Full text of DOI:10.1002/(sici)1099-0690(200005)2000:9<1685::aid-ejoc1685>3.0.co;2-6

FULL PAPER
1,3-Dipolar Cycloadditions, 116[‡]
The Formation of 1,3-Dithiolanes from Aromatic Thioketones and
Diazomethane ؊ The Mechanism of the Schönberg Reaction
Rolf Huisgen,*[a] Ivars Kalvinsch,[a][°] Xingya Li,[a][°°] and Grzegorz Mloston[a][°°°]
Dedicated to Christoph Rüchardt, Freiburg, on the occasion of his 70th birthday
Keywords: Thioketones / Thiocarbonyl ylides / Cycloadditions / Cycloreversions / Sulfur heterocycles
Reactions of diaryl thioketones with diazomethane at room
temperature afford 4,4,5,5-tetraaryl-1,3-dithiolanes; the
scope of this surprising 2:1 interaction has been studied for
decades (Schönberg Reaction). The clue to the mechanism
was our observation that the stoichiometry is 1:1 at −78 °C,
and 2,5-dihydro-2,2-diaryl-1,3,4-thiadiazoles are formed as
primary [2+3] cycloadducts. They lose N2 at −45 °C in first-
order reactions generating diaryl thioketone S-methylides
which can be intercepted by thioketones (Ǟ1,3-dithiolanes),
multiple CC bonds, or acids HX. In the absence of trapping
reagents, the elusive intermediates either dimerize furnish-
ing 2,2,3,3-tetraaryl-1,4-dithianes or give rise to 2,2-diaryl-
thiiranes by electrocyclization. Beyond thiobenzophenone
and diazomethane, our main model reaction, the studies in-
volve fluorene-9-thione, 4,4-dimethoxy- and 4,4-dichloro-
thiobenzophenone. The ring of 2,5-dihydro-2,2-diphenyl-
1,3,4-thiadiazole (8) is opened by LDA at −78 °C and deriva-
tives of anion 12 are obtained. − In summa: The Schönberg
reaction consists of two 1,3-dipolar cycloadditions, linked by
a 1,3-dipolar cycloreversion.
Introduction
In 1920 Staudinger and Siegwart have studied the reac-
tion of thiobenzophenone (1) with diphenyldiazomethane;
tetraphenylthiirane (2) was obtained in high yield.[1] Thio-
phosgen, thiobenzoyl chloride, diphenyl trithiocarbonate
and other thiocarbonyl compounds likewise reacted with
diphenyldiazomethane furnishing the corresponding thi-
iranes 3 (Scheme 1).[1,2]
Surprisingly, the reaction of 1 with diazomethane at 0° Ϫ
20 °C follows another stoichiometry. The formation of
4,4,5,5-tetraphenyl-1,3-dithiolane (4) was independently re-
ported in 1930/31 by Bergmann et al.[3] and Schönberg et
al.;[4] the diradical 5 was assumed to be a common interme-
diate on the pathway to thiirane and 1,3-dithiolane.[4] The
earlier proposals failed to consider that diazomethane is
stable in ether at 0 °C; the brisk evolution of N2 in the
interaction with 1 indicates an induced decomposition.
On varying thione and diazoalkane, SchönbergЈs group
observed that each pair produces either the thiirane or the
Scheme 1
dithiolane; the two were never found side by side. It was
baffling that, e.g., diphenyl trithiocarbonate afforded 6 with
diazomethane, and 7 with diazoethane.[5] Within four dec-
ades,[6] Schönberg returned repeatedly to the dichotomy of
pathways and its causes. A paper of 1967 reviewed the reac-
tions of 18 diazoalkanes with 32 thiocarbonyl com-
pounds;[7] the mechanistic conclusion was not encouraging:
"Regrettably, all attempts to elucidate the mechanism by the
isolation of intermediates or otherwise were in vain".[8]
In a preliminary report,[9] we found a sequence of two
1,3-dipolar cycloadditions, linked by a 1,3-dipolar cyclore-
version, to be responsible for the formation of 1,3-dithiol-
anes from thiones and diazo compounds; we named this
pathway to 1,3-dithiolanes the Schönberg Reaction.[10] We
[‡]
Part 115: R. Huisgen, G. Mloston, K. Polborn,
Heteroatom Chem. 1999, 10, 662Ϫ669.
[a]
Institut für Organische Chemie der Universität München,
Butenandtstrasse 13, D-81377 München, Germany
[°]
Present address: Latvian Institute of Organic Synthesis, Riga,
LV-1006, Latvia
[°°]
Present address: Avery Research Center, Pasadena, CA
91107, USA
[°°°] Present address: Institute of Organic and Applied Chemistry,
University of Lodz, Narutowicza 68, PL-90Ϫ136 Lodz,
Poland
Eur. J. Org. Chem. 2000, 1685Ϫ1694
WILEY-VCH Verlag GmbH, D-69451 Weinheim, 2000
1434Ϫ193X/00/0509Ϫ1685 $ 17.50ϩ.50/0
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R. Huisgen, I. Kalvinsch, X. Li, G. Mloston
FULL PAPER
give here the detailed description, supplemented by new
material and deeper insight.
Reagents which intercept the short-lived 9 do not inter-
vene in the rate-determining step, 8 ǞN2 ϩ 9. Dimethyl
acetylenedicarboxylate (DMAD), but not ethyl acetate, cap-
tures the 1,3-dipole affording the cycloadduct 10.[12] The
influence of these additives on the rate constant of N2
evolution was unsignificant and reflects small effects of sol-
vation. Furthermore, the rate process was undisturbed
when methanol and trifluoroacetic acid was added to the
THF solution of 8 (Table 1); the trapping of 9 with meth-
anol and acid will be described below.
The high reactivity of diazomethane to thiobenzo-
phenone requires brief comment. Diazomethane belongs to
the nucleophilic 1,3-dipoles; the rate constant of its cycload-
dition to ethyl acrylate has been measured between Ϫ20 °C
and Ϫ50 °C.[13] Even at Ϫ78 °C, thiobenzophenone was
found to react with diazomethane so fast, that the rate
could not be measured by conventional techniques. A low
LUMO energy is responsible for the superdipolarophilic
character of thiones.[14] Diphenyldiazomethane reacts 1260
times faster with 1 than with ethyl acrylate (DMF, 40
°C).[15]
2,5-Dihydro-2,2-diphenyl-1,3,4-thiadiazole (8) as
an Intermediate
The reaction of thiobenzophenone (1) with diazomethane
in THF or ether is remarkably fast even at Ϫ78 °C; in fact,
the deep-blue solution of 1 at Ϫ78 °C can be titrated (delay
by 2Ϫ3 s) by dropwise addition of a diazomethane solution
until the deep color disappeared, and the slightly yellow
color indicated the excess of diazomethane. The stoichi-
ometry was 1:1 and no N2 was evolved. When the reaction
took place in diethyl ether at Ϫ78 °C, the mixture solidified
to a crystalline mass of the cycloadduct 8 (Scheme 2). Iso-
lated colorless crystals of the 2,5-dihydro-2,2-diphenyl-
1,3,4-thiadiazole (8) are stable at Ϫ78 °C, but explode on
warming at about Ϫ20 °C.
Two regioisomers can result from 1,3-cycloadditions of
diazomethane to thiones Ϫ and they often do (see ref.[11]
and the ref. quoted there). Sterically hindered thioketones
prefer formation of the 2,5-dihydro-1,3,4-thiadiazoles,
which supports structure 8, not the 1,2,3-isomer 11
(Scheme 3).
Scheme 2
Since the addition of diazomethane to 1 proceeds quant-
itatively, there is no necessity to handle the crystals of 8. In
a routine operation, gaseous diazomethane was passed into
the solution of 10 mmol of 1 in THF at Ϫ78 °C, until the
1
blue color vanished. The H NMR spectrum of 8 (CDCl3,
Ϫ45 °C) shows the 5-H2 at δ ϭ 5.98, reflecting the shift to
higher frequencies by sulfur and azo functions. In the isol-
able spiro[adamantane-2,2Ј-thiadiazoline] (17) the δ(5Ј-H2)
was observed at 5.75.[11]
When the solution of thiadiazoline 8 was warmed from
Ϫ78 °C to Ϫ45 °C, one mol of N2 is evolved, and the short-
lived thiobenzophenone S-methylide (9) is set free. The N2
elimination followed first-order kinetics, and the half-life of
8 at Ϫ45 °C was volumetrically determined: 56 min in THF
and 57 min in CHCl3 (Table 1).
Scheme 3
There is direct evidence for structure 8. Deprotonation of
8 by 1.0 equiv. of LDA in THF at Ϫ78 °C and subsequent
hydrolysis gave rise to the yellow benzophenone Nβ-thiofor-
mylhydrazone (14, 44%), which is identical in melting point
Table 1. First-order rate constants for N2 evolution from 2,5-dihy-
dro-2,2-diphenyl-1,3,4-thiadiazole (8) at Ϫ45 °C
1
and H NMR parameters with a specimen which Zelenin
et al. obtained by thioformylation of benzophenone hy-
drazone.[16] The thioformyl group of 14 shows δH ϭ 9.72
and δC ϭ 189.6, in agreement with other thioformam-
ides.[17] The interaction of 14 with piperidine at 20 °C pro-
duced the light-yellow azine 16 (83%). When the lithium
salt, obtained from 8 and LDA, was treated with methyl
iodide, the (methylthiomethylene)hydrazone 15 was isol-
ated. The proton shift of NϭCH appears at δ ϭ 7.72 for
8 ()
Solvent and additives
104 k1 sϪ1
0.13
0.15
0.15
0.12
0.13
0.11
THF
CHCl3
2.03, 2.11
2.02
THF, 0.3  in ethyl acetate
THF, 0.3  in DMAD
THF, 0.4  in DMAD
THF, 5  in methanol, 0.1  in CF3CO2H
1.99
1.88
1.80
1.77
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1,3-Dipolar Cycloadditions, 116
FULL PAPER
15 and at δ ϭ 8.05 for 16. Conceivably, the anion of 8 is
already the ring-opened species 12.
Thiocarbonyl ylides are not new. Plenty of push-pull-sta-
bilized types are isolable,[24] but do not undergo cycloaddi-
Thioacylhydrazones of ketones undergo a ring-chain tau- tions. Short-lived representatives are intermediates (al-
tomerism with 2,3-dihydro-1,3,4-thiadiazoles.[16,18] In ac- though not recognized previously) in BartonЈs two-fold ex-
cordance with the Russian authors,[16] we found no evidence trusion process leading to highly hindered olefins.[25] The
for the appearance of 13. It is worth mentioning that the most versatile access to thiocarbonyl ylides is the N2 extru-
analogous treatment of the spiro[adamantane-2,2Ј-thiadia- sion from 2,5-dihydro-1,3,4-thiadiazoles; those from ali-
zoline] (17)[11] with LDA and protonation of the lithium phatic thioketones and diazoalkanes are isolable and have
salt furnished the cyclic ∆2-tautomer corresponding to limited storage capacity. Why does 8 enter into the cyclore-
13.[19]
version at as low a temperature as Ϫ45 °C? The transition
state of the cycloreversion reflects the stabilization of the
thiocarbonyl ylide 9 by phenyl conjugation.
Schönberg Reaction as Three-Step Procedure
1,3-Dipoles possess the π-MOs of the allyl anion. Since sul-
1.2 Equiv. of thiobenzophenone (1) were added to the fur has the same electronegativity as carbon, thiocarbonyl
solution of thiadiazoline 8 in THF at Ϫ78 °C. After 3 h in a ylides are expected to have MO energies not too far below
bath of Ϫ40 °C, the N2 evolution was complete and workup those of the allyl anion; they are nucleophilic 1,3-dipoles in
furnished SchönbergЈs tetraphenyl-1,3-dithiolane 4 in 95% SustmannЈs PMO concept of concerted cycloadditions.[26]
yield. When diazomethane was slowly introduced into the
Thiobenzophenone S-methylide (9) is a weak base. Nei-
solution of 1 in ether at 20 °C, a brisk evolution of nitrogen ther piperidine, aniline, methanol, or phenol interacted with
took place and likewise 95% of 4 was isolated; these are 9. However, when 9 was set free in methanolic 0.1  trifluo-
the reaction conditions, which led Bergmann et al.[4] and roacetic acid at Ϫ45 °C, the mixed O,S-dimethyl acetal 18
Schönberg et al.[4] to the discovery of 4.
was isolated in 83% yield. Both δH values, 1.63 for SCH3
The cleavage of thiadiazoline 8 into thiobenzophenone S- and 3.18 for OCH3, reveal some shielding by the phenyl
methylide (9) and N2 is a 1,3-dipolar cycloreversion. The groups. Thus, protonation of 9 initiates the reaction with
two-step sequence, CH2N2 ϩ 1 Ǟ 9 ϩ NϵN, can be re- methanol. An additional example is the reaction of 9 with
garded as a 1,3-dipole metathesis. The short-lived 1,3-dipole benzoic acid, which furnished 22% of the dimethyl di-
9 is intercepted by the second molecule of 1 in the conclud- thioacetal 19 and up to 71% of benzophenone; obviously,
ing 1,3-cycloaddition. Thus, the Schönberg reaction con- these are secondary products.
sists of a sequence of three cyclic six-electron processes (su-
pra-supra), which may be concerted in accord with the
WoodwardϪHoffmann rules.[20a] The process formally re-
sembles the conversion of alkene ϩ O3 Ǟ ozonide, that also
proceeds by two 1,3-dipolar cycloadditions, linked by a 1,3-
dipolar cycloreversion.
Head-Head Dimerization vs. Electrocyclization
In the absence of dipolarophiles, the N2 extrusion from 8
in THF at Ϫ40 °C furnished 95% of 2,2,3,3-tetraphenyl-
1,4-dithiane (21) and 1% of 1,1-diphenylethylene
(Scheme 4). The concerted combination of two 4π-systems
is forbidden by orbital control, but a twostep process ren-
ders the formation of the head-head dimer intelligible. Es-
tablishing of the first bond between the two methylene
groups allows the intermediate 20 a charge stabilization by
the phenyl groups; zwitterion and spin-coupled biradical
are probably synonymous here.
The stationary concentration of intermediate 8 in the
consecutive system is a function of the two rate constants,
k2 for the second-order cycloaddition and k1 for the first-
order cycloreversion (Scheme 2). Concerted cycloadditions
usually have low activation enthalpies and large negative
activation entropies.[21] The temperature coefficient, defined
as the ratio of rate constants upon an increase of 10 °C,
will be lower for k2 than for k1, the latter referring to a first-
order process with small activation entropy. On rising the
temperature, k1 will grow much faster than k2. As a general
rule, cycloadditions furnishing labile adducts should be run
at as low a temperature as feasible. This reasoning
prompted the elucidation of the Schönberg reaction by the
low-temperature experiment.
The mechanistic study opens up synthetic aspects. Sub-
sequent to the 1:1 reaction of 1 with diazomethane at Ϫ78
°C, other thiocarbonyl compounds can be added as di-
polarophiles. High yields of "mixed" 1,3-dithiolanes were
obtained in this widely variable synthesis.[22] It is the same
type of interception, which allowed the capture of 9 by
DMAD furnishing the dihydrothiophene derivative 10 in
Scheme 4
The typical AAЈBBЈ splitting pattern of 5-H2 and 6-H2
71% yield. It is chosen here as an example of the interaction in the 1H NMR spectrum of 21 at 25 °C indicates hindered
with a multitude of electron-deficient ethylenes and acetyl- ring inversion. Also the 13C signals of the four phenyl sub-
enes.[23]
stituents are pairwise different, whereas C-2/C-3 (δ ϭ 64.5)
Eur. J. Org. Chem. 2000, 1685Ϫ1694
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R. Huisgen, I. Kalvinsch, X. Li, G. Mloston
FULL PAPER
and C-5/C-6 (δ ϭ 31.4) give one signal each. The X-ray atures. Since 24 is the precursor of 25, the yields (in % of
analysis of the parent 1,4-dithiane disclosed a chair con- 8) were combined:
formation;[27] assuming the same conformation for 21, the
Table 2
point group C2 (21A) concords with the symmetry proper-
ties displayed in the NMR spectra. Further 2,2,3,3-tetra-
substituted 1,4-dithianes were recently obtained from thio-
Ϫ45 °C
Ϫ25 °C
0 °C
ϩ20 °C
carbonyl S-methylides, and confirmed by X-ray ana- dithiane 21
91
1.8
90
2.3
87
5.8
79
10.4
lyses.[28,29]
thiirane 24
1
The H NMR spectrum (60 MHz) of 21 in [D5]bromo-
benzene was studied in its dependence on temperature. Co-
alescence of the CH2 signals was reached at 74 °C, and a
singlet at δ ϭ 2.90 at 102 °C indicates the conversion of
AAЈBBЈ to A4. An approximate value of ∆G϶ ഠ 17.2 ± 0.6
kcal molϪ1 at 74 °C was calculated.
Barriers to ring inversion of the parent 1,3-dithiane and
1,2-dithiane, determined at low temperature,[30,31] are
slightly below that of cyclohexane (∆G϶ ϭ 10.2 kcal
molϪ1). For perfluoro-1,4-dithiane, ∆G϶ ϭ 10.1 kcal molϪ1
(TC at Ϫ33 °C) was measured by 19F NMR.[32] Thus, we
suppose that the slow process in the case of 21 comes from
the hindrance, which the proximal gem-diphenyl groups ex-
ert on the ring inversion.
Thiocarbonyl ylides, when not intercepted, usually un-
dergo an irreversible electrocyclization affording thiiranes.
The example 22 Ǟ 23, reported by Buter, Wassenaar, and
Kellogg,[33] elegantly established the conrotatory ring clos-
ure, a steric course, which was predicted by Woodward and
Hoffmann[20b] for the ring opening of cyclopropyl anions
to allyl anions. The adamantanethione S-methylide, origin-
ating from 17, cyclizes to the spirothiirane, and no dimer
was observed.[11] Thiobenzophenone S-methylide (9), how-
ever, either dimerizes giving 21 or undergoes electrocycliza-
tion forming 24, depending on stationary concentration
and temperature.
Since the two processes compete, the free energy changes
must be of the same order of magnitude. The dithiane
formation is burdened by the large negative ∆S϶ of bimo-
lecular processes. Therefore, ∆H϶, which controls the tem-
perature coefficient (see above) alone, must be greater for
the unimolecular ring closure 9 Ǟ 24. This is the reason for
a 5.8-fold increase of the thiirane pathway between Ϫ45 °C
and ϩ20 °C.
Schönberg, König et al. emphasized that each system of
thione and diazoalkane furnishes either the thiirane or the
1,3-dithiolane (2:1 product).[7] The statement needs revi-
sion. When the Schönberg procedure[4] was reversed, i.e.,
the solution of thiobenzophenone (1) slowly dropped into
the ether solution of 1 equiv. of diazomethane at 20 °C, 1H
NMR analysis showed the presence of 50% of 1,3-dithiol-
ane 4, 18% of dimer 21, and 22% of thiirane 24 (more pre-
cisely: 8% of 24 ϩ 14% of 25). Despite the low stationary
concentration of 1, still 50% of the S-methylide is inter-
cepted, an impressive demonstration for the high rate of the
cycloaddition, 9 ϩ 1.
Dithiolane 4 turns blue at the melting point, suggesting
a cycloreversion. When 4 was heated in CDCl3 for 35 h at
135 °C, conversion into diphenylethylene (25) amounted to
66%, i.e., the cycloreversion was followed by electrocycliza-
tion, 9 Ǟ 24, and desulfurization.
When 0.26  8 in THF, kept at Ϫ78 °C, was slowly intro-
duced into 1.5-fold the volume of THF at 20 °C, 55% of
dithiane 21 was isolated; H NMR analysis of the mother
liquor indicated 13% of 2,2-diphenylthiirane (24) and 25%
of 1,1-diphenylethylene (25) (Scheme 5). Repeated 1H
NMR recordings showed that the conversion 24 Ǟ 25 pro-
ceeded with a half-life of ഠ16 h. Many reagents, especially
thiolate anions,[34] catalyse the desulfurization of 24. Thus,
dimerization and electrocyclization of 9 took place in the
proportion ഠ 60:40.
Is it astonishing that the bimolecular dimerization, 2 ϫ 9
Ǟ 21, beats the unimolecular electrocyclization, 9 Ǟ 24?
The latter process is not as simple, as it appears at first
glance. The thiocarbonyl ylide 9 has a quasi-planar struc-
ture, and two 90° rotations about the CS bonds are required
for generating the new σ-bond. Thus, the resonance energy
of the thiocarbonyl ylide is sacrificed early on the energy
profile.
1
Thiobenzophenone S-Ethylide
The cycloaddition of diazoethane to 1 in THF at Ϫ78 °C
proceeded as smooth as that of the lower homolog. The
thiadiazoline 26 could be isolated, but the solid exploded
1
when the temperature rose above Ϫ40 °C. In the H NMR
spectrum at Ϫ65 °C, the 5-methyl appeared as doublet at
δH 1.89 and 5-H as quadruplet at 6.03. The 13C NMR spec-
trum reflects the diastereotopicity of the phenyl groups with
two sets of 4 aromatic C-signals.
Thiadiazoline 26 in THF expels N2 at Ϫ45 °C with a
half-life of 18 min, i.e., shorter than that of 8 by a factor of
Scheme 5
Control by temperature alone was determining when 0.1 3. Thiobenzophenone S-ethylide (27) cyclized to give 93%
 8 in THF was allowed to decompose at different temper- of the thiirane 28 and 3% of 1,1-diphenylpropene (29); the
1688
Eur. J. Org. Chem. 2000, 1685Ϫ1694

1,3-Dipolar Cycloadditions, 116
FULL PAPER
latter came from a partial desulfurization 28 Ǟ 29
We observed a rapid fading of the dark-green THF solu-
(Scheme 6). Thus, compared with the behavior of 9, the ad- tion of 31a upon addition of 1 equiv. of diazomethane at
ditional methyl group in the S-ethylide 27 is sufficient to Ϫ78 °C. N2 (95%) was liberated from the clear solution of
thwart the dimerization leading to a 1,4-dithiane. This ac- thiadiazoline 32a at Ϫ45 °C, and the colorless dimer 33a
cords well with our interpretation of dithiane formation via precipitated (Scheme 7). The N2 evolution at Ϫ45 °C fol-
the initial linkage by the methylene groups.
lowed the first-order with t1/2 ϭ 9.1 min; the rate constant
is 6 times greater than that of 8.
The high-melting 1,4-dithiane 33a has a low solubility.
1
The H NMR spectrum in [D5]pyridine or CDCl3 (dilute
solution) essentially features an AB pattern for 5-H2 and 6-
H2 with an apparent J ϭ 10.5 Hz; small satellites are indis-
tinct. The appearance of AAЈBBЈ spectra highly depends
on the ratio of the four coupling constants.
There is no sufficient reason to assume the head-tail
dimer 36a. Hindered inversion of 36a in the centrosym-
metric chair conformation should indeed give rise to an AB
spectrum for 3-H2/6-H2. However, with the separation of
the voluminous aromatic substituents in 36a the major
reason for hindrance would be gone. In the 13C NMR spec-
trum of 33a, the triplet of C-5/6 at δ ϭ 27.4 and the singlet
of C-2/3 at 55.4 disclose a shift to lower frequencies, com-
pared with the parameters of tetraphenyldithiane 21 (31.5,
64.5 ppm); the opposite would be expected for 36a, where
the methylene groups are flanked by sulfur and fluorenyl.
Some fragments in the MS are also better reconcilable with
33a than with 36a.
Scheme 6
In his 1931 report, Schönberg et al.[4] briefly mentioned
that 1,3-dithiolane 30 was obtained when diazoethane was
introduced into the solution of 1 at room temperature. This
protocol provided us with 87% of 30, accompanied by 5%
each of 28 and 29. The reverse procedure, i.e., the slow addi-
tion of 1 into the stirred solution of diazoethane at 20 °C,
reduced the yield of 30 to 29%, but promoted the electro-
cyclization: 40% of 28 and 28% of 29.
The C2v symmetry of 1,3-dithiolane 4 is reduced to Cs in
30. The phenyl groups located cis and trans to the 5-CH3
are pairwise different, as revealed by the 13C NMR para-
meters.
4,4Ј-Dimethoxy- and
4,4Ј-Dichlorothiobenzophenone S-Methylide
Fluorene-9-thione S-Methylide
1,3-Dipoles 35b and 35c were only briefly studied. Both
prefer head-head dimerization to the electrocyclic ring clos-
ure.
Schönberg, König et al.[7] isolated 92% of the 1,3-dithiol-
ane 34a, when diazomethane was added to fluorene-9-
thione (31a) in ether at room temperature; the reduction of
34a with zinc and acid furnished 9,9Ј-bifluorenyl (37a). We
confirmed the high yield of 34a and used Raney nickel in
methanol for the hydrogenolysis. The 2-H2 of 34a resonates
at δ ϭ 4.70. The 13C NMR parameters accord with the
point group C2v; there are six aromatic C-signals (4d ϩ 2s),
and the s of C-4/C-5 appears at δ ϭ 74.2.
When ethereal diazomethane was added portionwise to
0.2  4,4Ј-dimethoxythiobenzophenone (31b) in ether at
room temperature, the disappearance of the deep-blue color
was markedly slower than observed for 1. That is not unex-
pected. According to rate measurements for the cycloaddi-
tions of diphenyldiazomethane, the electron-releasing 4-me-
thoxy groups in 31b deactivate thiobenzophenone by a fac-
tor of 28 (CHCl3, 40 °C).[15]
Bergmann et al.[3] reported in 1930 already on the forma-
tion of 1,3-dithiolane 34b (49%) and established its regio-
chemistry by treatment with zinc and acid, producing tetra-
anisylethylene (38b). We isolated the crystalline 34b in 93%
yield; the desulfurization by Raney nickel in methanol like-
wise halted at 38b (94%).
At Ϫ78 °C, the interaction of 31b with diazomethane re-
quired 7 h; that is very slow compared with the titration of
1 with diazomethane. The N2 loss from the thiadiazoline
32b in THF at Ϫ45 °C was measured by volumetry (t1/2
36.8 min). Dimerization of the S-methylide 35b was ob-
served; the AAЈBBЈ spectrum for 5-H2/6-H2 of the 1,4-di-
thiane 33b left no doubt about the structure element
ϪCH2ϪCH2Ϫ in the ring.
4,4Ј-Dichlorothiobenzophenone (31c) accepted diazo-
methane rapidly at Ϫ78 °C. Like the other 1,4-dithianes,
Scheme 7
Eur. J. Org. Chem. 2000, 1685Ϫ1694
1689

R. Huisgen, I. Kalvinsch, X. Li, G. Mloston
FULL PAPER
Gaseous diazomethane, diluted by N2,[36] was passed into the solv-
ent to prepare the solutions used above; the concentration was de-
termined by reacting an aliquot with a weighed excess of benzoic
acid in ether and back-titration with 0.1  NaOH.[37] A still simpler
access to 8 was the passing of gaseous diazomethane into the solu-
tion of 10 mmol of 1 in 30 mL of THF at Ϫ78 °C, until the deep-
blue color turned to light-yellow. The slight excess of diazomethane
can be removed by adding a small amount of 1. The stock solution
was divided into aliquots to study the reactions of 8.
33c (82%) is slightly soluble. The NMR evidence for the
structure is conclusive. Apart from the AAЈBBЈ spectrum of
5-H2/6-H2 which stretches over 0.5 ppm, the 13C parameters
reveal the equivalence of the pairs C-5/6 (t at δ ϭ 31.2) and
C-2/3 (s at δ ϭ 63.1). The four 4-chlorophenyl groups are
pairwise in different environments, in accordance with C2
symmetry.
Kinetic Measurement of the N2 Extrusion by Nitrometry: The mag-
netically stirred solution of about 3 mmol of 8 in 20 mL of THF,
prepared at Ϫ78 °C, was placed into a bath of Ϫ44.8 ± 1 °C (ther-
mostat) and connected with a 100 mL nitrometer. The reading of
the N2 volume after 20 min defined Vo, and Vϱ was determined
after 10 h (and corrected when necessary). The first-order law,
k t ϭ ln (Vϱ/Vϱ-Vt), was strictly followed, at least for two half-
Experimental Section
General: IR: PerkinϪElmer 125. Ϫ NMR: Varian A60 for 1H
(60 MHz) and Varian XL 100 for 1H (100 MHz) and 13C
(25.2 MHz); Bruker WP 80 for 13C (20.2 MHz). TMS was used as
internal standard and acid-free CDCl3 (stored over dry K2CO3) as
solvent, if not otherwise stated. Ϫ The MS are EI spectra with
70 eV, recorded with MS 902 of AEI, Manchester; some recent re-
cordings with MAT 90 gave peak intensities (isotope peaks) with
higher precision. Isotope peaks are given in the form, e.g., 13C%
calcd./found. Ϫ PLC is thick-layer (1 or 2 mm) chromatography on
silica gel, usually Merck F254. Ϫ Melting points are uncorrected.
lives. Two runs (0.14 and 0.13  8) provided 104 k2: 2.11, 2.03 sϪ1
;
linear regression of 25 readings up to 105 min gave a correlation
with r ϭ 0.999. In the same way, the other experiments of Table 1
were performed.
Deprotonation of 8: 3.0 mmol of 8 in 50 mL of abs. THF were
flushed with argon at Ϫ78 °C and treated portionwise with
3.1 mmol of LDA in 25 mL of THF, freshly prepared from diiso-
propylamine and butyllithium. After allowing the solution to come
to room temp., the solvent was evaporated, and the lithium salt 12
treated with 50 mL of water and 25 mL of CH2Cl2. Workup of the
organic phase furnished 315 mg (44%) of benzophenone N-thiofor-
mylhydrazone (14); the yellow prisms were recrystallized from eth-
anol, m.p. 122Ϫ123 °C (122Ϫ124 °C).[16] Ϫ UV (CH2Cl2): λmax
(log ε) ϭ 3.31 (4.57), 241 (4.04). Ϫ IR (KBr): ν˜ ϭ 691, 699, 779 st
(C6H5 out-of-plane deform.), 1279, 1302, 1328 st; 1492 st, 1510 vst
(arom. ring vibr., CϭN), 3135 m, 3290 w (NϪH); (CHCl3): 3290
m (NϪH). Ϫ 1H NMR: δ ϭ 7.05Ϫ7.92 (m, 2 C6H5). 9.72 (s, HCϭ
S; 9.66[16]). Ϫ 13C NMR: δ ϭ 128.0, 128.4, 128.5 (3 d, 10 arom.
CH), 135.9 (s, 2 C-1 of C6H5), 155.2 (s, CϭN; 155.5[16]), 189.6 (d,
CHS). Ϫ MS (70 °C); m/z (%): 240 (30) [Mϩ], 180 (100) [no 34S
peak, probably C6H5ϪCϵNϩϪC6H5), 163 (90) [Mϩ Ϫ C6H5]. Ϫ
C14H12N2S (240.3): calcd. C 69.97, H 5.03, N 11.66, S 13.34; found
C 69.92, H 5.11, N 11.50, S 13.24.
Thioketones are subject to autoxidation; all operations were carried
out under a nitrogen or argon atmosphere.
2,5-Dihydro-2,2-diphenyl-1,3,4-thiadiazole (8) and Thiobenzo-
phenone S-Methylide (9)
Dimethyl 2,2-Diphenyl-2,5-dihydrothiophene-3,4-dicarboxylate (10):
The magnetically stirred solution of 1.14 g (5.75 mmol) of thioben-
zophenone (1)[35] in 20 mL of THF was cooled to Ϫ78 °C (acetone/
CO2 bath) under N2; 6 mL of ഠ 1.0  diazomethane[36] in THF
was introduced slowly so as to diminish the increase of temper-
ature. When the color of the dark-blue solution lightened, the resid-
ual diazomethane solution was added dropwise. The titration
worked with a delay of 2Ϫ3 s per drop; the solution became color-
less and then yellow-tinged by the excess of diazomethane. 1.63 g
(11.5 mmol, 2 equiv) of dimethyl acetylenedicarboxylate (DMAD)
in 8 mL of THF, precooled to Ϫ78 °C, was added, and the solution
was kept in a bath at Ϫ40 °C (low-temp. thermostat) overnight.
After removal of the solvent, the residue was triturated with little
methanol, and 1.41 g of colorless crystals, m.p. 137Ϫ139.5 °C, were
filtered. The mother liquor was brought to dryness by distilling
solvent and excess of DMAD in vacuo. A second crop of 10
(38 mg, total yield 71%) was obtained from 1 mL of methanol. The
analytical specimen was recrystallized from ether, m.p. 140Ϫ142
°C. Ϫ 1H NMR: δ ϭ 3.40, 3.73 (2 s, 2 OCH3), 4.04 (s, 5-H2),
7.2Ϫ7.6 (m, 2 C6H5). Ϫ 13C NMR (20.2 MHz): δ ϭ 36.2 (t, C-5),
52.2, 52.5 (2 q, 2 OCH3), 74.9 (s, C-2), 127.3, 127.9, 128.6 (3 d, 10
arom. CH), 135.2, 143.2, 148.1 (3 s, C-3, C-4, 2 C-1Ј), 163.4, 165.1
(2 s, 2 CϭO). Ϫ C20H18O4S (354.4): calcd. C 67.77, H 5.12, S 9.05;
found C 68.04, H 5.19, S 9.01.
Lithium Salt 12 and Methyl Iodide: 12, prepared from 3.0 mmol of
8, as described above, was refluxed with 5 mL of methyl iodide
for 1.5 h. Workup with 5% aqueous ammonia/CH2Cl2 and PLC
(acetone/petroleum ether, 3:7) furnished 365 mg (48%) of benzo-
phenone Nβ-(methylthiomethylene)hydrazone (15), m.p. 80Ϫ82 °C
(ethanol). Ϫ UV (CH2Cl2): λ ϭ 302 (4.14), 238 (4.27). Ϫ IR (KBr):
ν˜ ϭ 692, 702, 764, 779 st (C6H5 out-of-plane deform.), 1446, 1495
1
m, 1556 st br (arom. ring vibr., CϭN). Ϫ H NMR: δ ϭ 2.40 (s,
SCH3), 7.07Ϫ7.47 (m, 8 arom. CH), 7.52Ϫ7.70 (m, 2 arom. CH),
7.72 (s, HCϭN). Ϫ MS (70 °C); m/z (%): 254 (30) [Mϩ], 180 (90)
[C6H5ϪCϵNϩϪC6H5)], 77 (100) [C6H5ϩ]. Ϫ C15H14N2S (254.3):
calcd. C 70.83, H 5.55, N 11.02, S 12.61; found C 71.20, H 5.65,
N 10.90, S 12.71.
Isolation of Thiadiazoline 8: The reaction above could also be car-
ried out by the inverse procedure, i.e., by adding the solution of 1
to the diazomethane solution which was magnetically stirred in a
Ϫ78 °C bath. This "titration" was even more sensitive; a persistent
blue indicated the passing of the point of equivalence. In an experi-
ment in diethyl ether as solvent, 8 crystallized and was suctionfil-
Benzophenone Nβ-(Piperidinomethylene)hydrazone (16): 240 mg
(1.00 mmol) of 14 was dissolved in 5 mL of piperidine (10 h, 20
°C). Workup with water/CH2Cl2 and PLC (CH2Cl2/ethanol 99:1)
afforded 241 mg (83%) of 16 as a light-yellow oil. Ϫ IR (film): ν˜ ϭ
694, 732, 769, 777 st (C6H5 out-of-plane deform.), 1450 st br, 1494
tered on a precooled funnel. After washing with little precooled st, 1544 st br, 1618 vst br (C6H5 ring vibr., CϭN). Ϫ 1H NMR:
ether and pumping off the solvent, the colorless 8 was stable at
Ϫ78 °C. When the cooling was shut off, the specimen rapidly de-
composed with gas evolution at about Ϫ20 °C.
δ ϭ 1.42Ϫ1.75 (m, 3 CH2), 3.15Ϫ3.40 (m, 2 NCH2), 7.12Ϫ7.42 (m,
8 arom. H), 7.42Ϫ7.65 (m, 2 arom. H), 8.05 (s, HCϭN). Ϫ MS (70
°C); m/z (%): 291 (43) [Mϩ], 182 (81), 111 (60), 84 (90) [C5H10Nϩ],
1690
Eur. J. Org. Chem. 2000, 1685Ϫ1694

1,3-Dipolar Cycloadditions, 116
FULL PAPER
83 (100) [C5H9Nϩ], 77 (48) [C6H5ϩ]. Ϫ C19H21N3 (291.4): calcd. C
78.31, H 7.26, N 14.42; found C 78.30, H 7.37, N 14.16.
zoic acid. Ϫ In a second experiment with 2.50 mmol of 8 and
3.0 mmol of benzoic acid, the reaction solution was neutralized
with 0.1  NaOH. Workup with water/ether afforded 322 mg (71%)
of benzophenone, m.p. 47Ϫ48 °C (pentane).
4,4,5,5-Tetraphenyl-1,3-dithiolane (4). ؊ (a): 3.96 g (20.0 mmol) of
1 in 20 mL of ether was treated portionwise with 14 mmol of diazo-
methane in 20 mL of ether at room temp. When the N2 evolution 2,2,3,3-Tetraphenyl-1,4-dithiane (21). ؊ (a): 11.1 mmol of 8 in
ceased and the dark-blue color turned yellow, the excess of diazo-
methane was destroyed by some drops of acetic acid; on concentra-
tion to ഠ 10 mL, 3.90 g (95%) of colorless 4 deposited, m.p.
25 mL of THF was prepared at Ϫ78 °C; 8 partially crystallized and
dissolved with rising temperature. On warming to Ϫ40 °C (1 h) and
keeping at Ϫ30 °C over night, N2 was evolved, and the crystalliza-
205Ϫ207 °C (blue melt; 199Ϫ200 °C[4]). Ϫ (b): 654 mg (3.30 mmol) tion of the colorless 21 took place; in two fractions 2.24 g (95%)
of 1 in 10 mL of THF was "titrated" at Ϫ78 °C with diazomethane
in THF, and 800 mg (4.03 mmol) of 1 in 5 mL of THF was added.
After 4 h at Ϫ40 °C and several h at room temp., workup furnished
1281 mg (95%) of 4, m.p. 203Ϫ204 °C (dec., blue). Ϫ 1H NMR:
δ ϭ 3.66 (s, 2-H2), 6.45Ϫ7.49 (m, 2 C6H5). Ϫ C27H22S2 (410.6):
was obtained, m.p. 145Ϫ150 °C (dec.) and, recrystallized from
CHCl3, m.p. 166Ϫ169 °C (dec.); the mother liquor contained 1.2%
of 1,1-diphenylethylene (25, NMR analysis see below). Crystalline
21 turns violet in sunlight. Ϫ 1H NMR (CDCl3): δ ϭ 2.44Ϫ3.70
(AAЈBBЈ, 12 lines visible at 25 °C, 5-H2, 6-H2), 6.7Ϫ7.8 (m, 20
calcd. C 78.98, H 5.40, S 15.62; found C 79.17, H 5.65, S 15.63. Ϫ arom. H); ([D5]bromobenzene, 60 MHz): 2.32Ϫ3.46 (AAЈBBЈ at
(c) Hydrogenolysis: 800 mg (1.95 mmol) of 4 were refluxed in
50 mL of methanol with 15 g of Raney nickel for 4 d. Hot filtering,
washing with 200 mL of CHCl3, and evaporation of the solvent
furnished 580 mg (90%) of tetraphenylethylene, m.p. 222Ϫ223 °C.
ϩ35 °C); broadens on increase of temp. and reaches coalescence at
ϩ74 °C; at 102 °C s δ ϭ 2.90 (A4); (400 MHz): δ ϭ 2.56, 3.14 (2
d ϩ satellites, AAЈXXЈ, Jappar. ϭ 9.8 Hz). Ϫ 13C NMR (CDCl3,
20.2 MHz): δ ϭ 31.4 (t, C-5/6), 64.5 (s, C-2/3), 125.2, 126.4, 126.8,
131.9, 134.5 (5 d, 20 arom. CH for 2 pairs of diastereotopic C6H5),
144.7, 146.3 (2 s, 2 C-1Ј of 4 C6H5). Ϫ MS (70 °C); m/z (%): 424
(1.6) [Mϩ], 332 (11) [Mϩ Ϫ 92, C26H2ϩ0; 13C 3.3/3.1], 230 (6)
[C13H10S2ϩ ?], 229 (7), 198 (90) [1ϩ; 13C 13/14, (34Sϩ13C2) 4.9/4.7],
α-Methoxy-α-(methylthio)diphenylmethane (18). ؊ (a): 4.32 mmol
of thiadiazoline 8 in 14 mL of THF at Ϫ78 °C was added to 0.2 mL
(2.7 mmol) of trifluoroacetic acid in 10 mL of methanol, precooled
to Ϫ78 °C. After 6 h at Ϫ45 °C, the solution was neutralized by
dropwise addition of methanolic KOH. The solvent was removed
at the rotary evaporator at room temp. and the residue triturated
with 10 mL of pentane and filtered. Distillation of the pentane,
finally at high vacuum, left 877 mg (83%) of a colorless oil which
165 (100) [9-fluorenylϩ, 13C 14.5/14.6], 121 (61) [C6H5ϪCϵSϩ; 13
C
4.8/5.1; (34Sϩ13C2) 2.9/2.9], 105 (11) [C8H9ϩ, α-phenylethylϩ ?], 77
(22) [C6H5ϩ]. Ϫ C28H24S2 (424.6): calcd. C 79.20, H 5.70, S 15.10;
found C 79.32, H 5.60, S 15.11.
was almost pure 18 according to the NMR spectra. The analytical (b) Determination of the Barrier to Ring Inversion: Based on 9 vis-
1
1
specimen was purified by PLC (CHCl3/petroleum ether 1:1). Ϫ H
ible lines, due to 5-H2/6-H2, in the H NMR spectrum (60 MHz)
NMR: δ ϭ 1.63 (s, SCH3), 3.18 (s, OCH3), 7.0Ϫ7.6 (m, 2 C6H5).
Ϫ
of 21 in [D5]bromobenzene, the AAЈBBЈ pattern was simulated by
13C NMR: δ ϭ 10.4 (q, SCH3), 50.4 (q, OCH3), 94.1 (s, Cq), the program Numarit[38] (in Hz); νA ϭ 156.6, νB ϭ 190.0, Jgem
ϭ
127.0 (d, C-2/6 ϩ C-3/5 of 2 C6H5), 127.7 (d, C-4 of 2 C6H5), 143.6
Ϫ13.0 Hz, and Jvic ϭ 12.6, 2.8, 1.9 Hz; ∆ν ϭ 33.4 Hz. In the
(s, C-1 of 2 C6H5). Ϫ MS (30 °C); m/z (%): 213 (0.5) [Mϩ Ϫ OCH3], 400 MHz spectrum, TC is expected around 100 °C; massive decom-
197 (6) [Mϩ Ϫ SCH3], 182 (41) [(C6H5)2COϩ], 167 (5) [Mϩ
Ϫ
position of 21 started even earlier. Therefore, we used the 400 MHz
C6H5], 105 (100) [C6H5ϪCϵOϩ], 77 (53) [C6H5ϩ]. Ϫ C15H16OS parameters only to determine the temperature dependence of ∆ν
(244.3): calcd. C 73.73, H 6.60, S 13.12; found C 73.66, H 6.35,
S 13.13.
(transformed to 60 MHz) in Hz (°C): 34.9 (25), 34.6 (45), 34.2 (65).
The rate constant of ring inversion was calculated with ∆v ϭ
34.0 Hz at TC ϭ 74 °C by the expression for AB spectra:[39] kC
ϭ
1
(b) Disproportionation of 18: When the H NMR spectrum of the
π[0.5 (∆ν2 ϩ 6 J2AB)]1/2 ϭ 103 sϪ1
The free energy change amounts to 17.2 ± 0.6 kcal molϪ1
.
above sample was recorded again after 1 and 2 weeks, the signals
of α,α-bis(methoxy)diphenylmethane (δ ϭ 3.08, s, 2 OCH3) and
α,α-bis(methylthio)diphenylmethane (19, δ ϭ 1.80, 2 SCH3) ap-
peared, indicating a partial disproportionation.
.
(c): 3.8 equiv. of piperidine was added to the THF solution of 8 at
Ϫ78 °C. The N2 expulsion took place at Ϫ40 °C, and workup af-
forded 84% of dithiane 21. Corresponding experiments with 2
equiv. of phenol or aniline yielded 71% and 72% of 21, respectively.
(c) 8 and Methanol Without Acid: 500 mg (2.52 mmol) of 1 in 5 mL
of THF at Ϫ78 °C was converted into 8 and mixed with 20 mL of
precooled methanol. The 1,4-dithiane 21 precipitated during the
reaction at Ϫ40 °C: 450 mg (84%), m.p. 166Ϫ169 °C.
Competition of Dimerization and Electrocyclization for 10. ؊ (a):
From a double-jacketed dropping funnel, cooled to Ϫ78 °C, the
8 and Benzoic Acid: 4.04 mmol of 8 in 15 mL of THF at Ϫ78 °C solution of 8 (3.16 mmol) in 12 mL of THF was introduced within
was reacted with 541 mg (4.43 mmol) of benzoic acid for 5 h at
Ϫ40 °C. Evaporation of the solvent left a foul-smelling oil which
was subjected to PLC (CHCl3). The first fraction furnished 115 mg
20 min into 20 mL of THF, magnetically stirred. After concentra-
tion at the rotary evaporator, 5 mL of petroleum ether was added
and 366 mg (55%) of 21 was filtered. The residue of the mother
1
(22%) of 19 as light-yellow crystals, m.p. 68Ϫ70 °C (pentane). Ϫ liquor was H NMR analyzed (CDCl3) with stilbene (δH ϭ 6.47)
IR (KBr): ν˜ ϭ 694, 736 st (C6H5 out-of-plane deform.), 1445, 1496 as weight standard: 91 mg (14%) of 2,2-diphenylthiirane (24, δH
ϭ
m, 1592 w (C6H5 ring vibr.). Ϫ 1H NMR: δ ϭ 1.81 (s, 2 SCH3), 2.98) and 143 mg (25%) of 1,1-diphenylethylene (25, δH ϭ 5.38). Ϫ
7.05Ϫ7.56 (m, 2 C6H5). Ϫ 13C NMR: δ ϭ 13.3 (q, 2 CH3), 69.5 (s,
Cq), 127.0 (d, 2 C-4), 127.8. 128.4 (2 d, 2 C-3/5, 2 C-2/6), 143.5 (s,
(b): The solution of 4.0 mmol of 8 in 11 mL of THF, prepared at
Ϫ78 °C, was mixed under stirring with 29 mL of THF, thermo-
stated in a Ϫ45° bath. After 5 h at Ϫ45 °C the THF was evaporated
2 C-1). Ϫ MS (30 °C); m/z (%): 260 (3) [Mϩ], 213 (100) [Mϩ
Ϫ
SCH3], 165 (31) [9-fluorenylϩ], 121 (26) [C6H5ϪCϵSϩ], 77 (7) at room temp., and the residue triturated with 10 mL of ether/pet-
[C6H5ϩ]. Ϫ C15H16S2 (260.4): calcd. C 69.18, H 6.19, S 24.63; found roleum ether (1:1). 21 (772 mg) remained undissolved; a second
C 69.57, H 6.23, S 24.62. Ϫ The second PLC fraction afforded
258 mg (35%) of benzophenone, m.p. 47.5Ϫ48.5 °C (pentane), and
the third fraction (eluted by methanol) consisted of 237 mg of ben-
fraction of 15 mg included, the yield ot 21 was 91%. The 1H NMR
analysis (CDCl3) of the mother liquor indicated 0.07 mmol of (24
ϩ 25, 1.8%). Three analogous experiments at Ϫ25 °C (2 h), 0 °C
Eur. J. Org. Chem. 2000, 1685Ϫ1694
1691

R. Huisgen, I. Kalvinsch, X. Li, G. Mloston
FULL PAPER
(1 h), and 20 °C (30 min) afforded the yields listed in Table 2. Ϫ
(c): 758 mg (3.82 mmol) of 1 in 10 mL of ether was dropped into
the stirred solution of 3.8 mmol of diazomethane in 20 mL of ether
at room temp. within 30 min. The residue after evaporation was
triturated with ether/petroleum ether as above; 537 mg of colorless
powder consisted of 390 mg (50%) of 4 and 140 mg (17%) of 21,
The mother liquor was evaporated. 1H NMR analysis (CDCl3)
with N,N-dimethylaniline as weight standard indicated 5% of 28
and 5% of 29. Ϫ (b): Ethereal 0.35  1 was dropped into the stirred
solution of 2.04 mmol of diazoethane in 10 mL of ether at room
temp., until the color had changed to light-blue. Workup as above
1
gave 247 mg (29%) of 30 and the H NMR analysis revealed 40%
of 28 and 28% of 29 (all yields based on diazoethane).
1
as the H NMR analysis (CDCl3, 2-methylnaphthalene as weight
standard, δ ϭ 2.42) of the CH2 signals indicated. The oily residue
of the mother liquor contained 8% of 24 and 14% of 25 (all yields
based on 1). Ϫ (d): 42.4 mg (103 µmol) of 4 in 0.5 mL of CDCl3
was heated in a closed NMR tube to 135 °C for 35 h. The CH2
signal of 4 had disappeared, and 66% of 25 was formed; the deep-
blue color comes from the liberated 1.[40]
Fluorene-9-thione S-Methylide (35a)
Dispiro[1,3-dithiolane-4,9Ј;5,9ЈЈ-bis(fluorene)] (34a). ؊ (a): Fluor-
ene-9-thione (31a, 1.96 g, 10.0 mmol) in 25 mL of ether at room
temp. was treated portionwise with an excess of ethereal diazo-
methane, until the dark-green color turned yellow, and became col-
orless, when a few drops of acetic acid were added. After concentra-
tion to ഠ 10 mL, 1.90 g (94%) of colorless 34a deposited, m.p.
259Ϫ262 °C (dec., red melt; 253Ϫ256 °C[7]) after recrystallization
from toluene. Ϫ 1H NMR: δ ϭ 4.70 (s, 2-H2), 6.9Ϫ7.6 (m, 16 arom.
H). Ϫ 13C NMR (25 MHz): δ ϭ 32.4 (t, C-2), 74.2 (s, C-4/5), 119.1,
126.4, 126.5, 128.3 (4 d, 16 arom. CH), 140.0, 144.5 (2 s, 8 arom.
Cq).
5-Methyl-2,2-diphenyl-2,5-dihydro-1,3,4-thiadiazol (26)
1 and Diazoethane. ؊ (a): 1 (752 mg, 3.79 mmol) in 7 mL of
CH2Cl2 was cooled to Ϫ78 °C and mixed with the precooled solu-
tion of 1 equiv. of diazoethane in 5.6 mL of CH2Cl2. The dark-
blue color vanished within several s, and thiadiazoline 26 partially
precipitated. N2 evolution took place at Ϫ40 °C. After warming to
1
room temp., the solvent was removed, and the oil subjected to H
(b) Hydrogenolysis: 1.02 g (2.51 mmol) of 34a and 20 g of Raney
nickel (Merck, activated) were refluxed in 100 mL of methanol for
4 d. Hot filtration, washing with CHCl3, and evaporation of the
solvent gave 580 mg (70%) of 9,9Ј-bifluorenyl (37a), colorless crys-
NMR analysis: 93% of 3-methyl-2,2-diphenylthiirane (28) and 3%
of 1,1-diphenylpropene (29). The desulfurization 28 Ǟ 29 (catalysts
unknown) was slow at room temp.; t1/2 ഠ 400 h was estimated from
1
1
repeated H NMR measurements. Ϫ H NMR of 28: δ ϭ 1.24 (d,
1
tals, m.p. 248Ϫ249 °C (CHCl3), 246Ϫ247 °C.[7] Ϫ H NMR: δ ϭ
J ϭ 6.0 Hz, CH3), 3.62 (q, J ϭ 6.0 Hz, 3-H), 6.9Ϫ7.4 (m, 2 C6H5).
Ϫ
13C NMR of 28: δ ϭ 18.8 (q, CH3), 42.9 (d, C-3), 59.6 (s, C-2),
4.83 (s, 2 benzylic H), 6.83Ϫ7.75 (m, 16 arom. H). Ϫ MS (90 °C);
m/z (%): 330 (15) [Mϩ], 165 (100) [C13H9ϩ, 9-fluorenylϩ; 13C 15/13].
126.8, 127.1, 2 ϫ 127.7, 128.0, 130.2 (6 d, 10 arom. CH; 2
diastereotopic C6H5), 138.8, 144.6 (2 s, 2 C-1Ј of 2 C6H5). Ϫ 1H
NMR of 29: δ ϭ 1.68 (d, J ϭ 7.0 Hz, CH3), 6.10 (q, J ϭ 7.0 Hz,
2-H), 7.0Ϫ7.6 (m, 2 C6H5).
Dispiro[1,4-dithiane-2,9Ј;3,9ЈЈ-bis(fluorene)] (33a). ؊ (a): 655 mg
(3.34 mmol) of 31a in 10 mL of THF was cooled to Ϫ78 °C. The
dark-green color faded upon slow addition of 1 equiv. of diazo-
methane in ഠ 1 min. No N2 evolution was observed at Ϫ78 °C;
when the clear solution was placed in a Ϫ45 °C bath, 79.5 mL of
N2 (3.14 mmol, 95%) were liberated within 2 h, and a colorless
powder precipitated. Removal of the solvent at the rotary evapor-
ator left 625 mg (89%) of 33a, m.p Ͼ 250 °C (dec.), which has a
low solubility in the usual solvents. Recrystallization from benzene
furnished colorless platelets, m.p. Ͼ 260 (dark-red black). Ϫ 1H
NMR ([D5]pyridine): δ ϭ 3.13, 4.16 (nearly AB, J ϭ 10.5 Hz, 5-
H2/6-H2), 6.1Ϫ7.6 (16 arom. H); (CDCl3, 100 MHz): 3.07, 4.07
(AB, J ϭ 10.4 Hz, 5-H2/6-H2), 6.05Ϫ7.56 (m, 16 arom. H); due to
the low solubility, the satellites expected for AAЈBBЈ are not very
distinct. Ϫ 13C NMR (CDCl3, 20 MHz): δ ϭ 27.4 (t, C-5/6), 55.4
(s, C-2/3), 119.0, 120.2, 125.2, 126.3, 126.5, 127.7, 2 ϫ 128.3 (8 d,
16 arom. CH), 139.7, 140.2, 144.0, 149.5 (4 s, 8 arom. Cq). Ϫ MS
(140 °C); m/z (%): 420 (26) [Mϩ; 13C 8.2/8.1, (34Sϩ13C2) 3.6/3.5],
360 (2) [Mϩ Ϫ SC2H4, C26H16Sϩ; 13C 0.54/0.56, (34Sϩ13C2) 0.16/
0.13], 328 (16) [C26H1ϩ6, 9,9Ј-bifluorenylideneϩ; 13C 4.5/4.1, no 34S
(b) NMR spectra of 26: A solution of 26 in CDCl3 was prepared
at Ϫ78 °C. Ϫ 1H NMR (100 MHz, Ϫ65 °C): δ ϭ 1.89 (d, J ϭ
7.0 Hz, 5-CH3), 6.03 (q, J ϭ 7.0 Hz, 5-H), 7.2Ϫ7.6 (m, 2 C6H5). Ϫ
13C NMR (25 MHz, Ϫ60 °C, signals of 28 deducted): δ ϭ 20.3 (q,
CH3), 95.7 (d, C-5), 116.0 (s, C-2), 126.9, 127.0, 127.1, 128.1, 128.2
(5 d, 10 arom. CH of 2 diastereotopic C6H5), 139.6, 142.3 (2 s, 2
C-1Ј of 2 C6H5).
Kinetics of N2 Evolution: The volumetric rate measurement at Ϫ45
°C was carried out as described above for 8. 0.15  26 in THF
afforded k1 ϭ 6.34 10Ϫ4 sϪ1
.
2-Methyl-4,4,5,5-tetraphenyl-1,3-dithiolane (30). ؊ (a): The orange
0.5  solution of diazoethane in ether was dropwise added to the
stirred solution of 995 mg (5.02 mmol) of 1 in 7 mL of THF at
room temp., until the dark-blue color had faded. After removal of
the solvent, the residue crystallized from ether/pentane (1:1):
924 mg (87%) of colorless 30, m.p. 172Ϫ174 °C (dec., blue); ref.[4]
:
peak], 327 (16), 326 (12), 210 (6) [C14H10Sϩ, 35aϩ or Mϩϩ 13C
;
1
no yield given, m.p. 170Ϫ172 °C. Ϫ H NMR: δ ϭ 1.65 (d, J ϭ
6.3 Hz, CH3), 4.09 (q, 2-H), 6.9Ϫ7.6 (m, 10 arom. H). Ϫ 13C NMR
(20 MHz): δ ϭ 18.4 (q, CH3), 42.7 (d, C-2), 79.6 (s, C-4/5), 126.1,
126.2, 126.4, 126.6, 131.3, 132.0 (6 d, 2 diastereotopic pairs of
C6H5), 142.9, 143.9 (2 s, 4 C-1Ј of C6H5). Ϫ MS (80 °C); m/z (%):
424 (1.3) [Mϩ], 332 (17) [Mϩ Ϫ CH2S2, (C6H5)2CϭC(C6H5)2ϩ or
isomer; 13C 5.0/4.8, 13C2 0.7/0.6], 255 (4) [332 Ϫ C6H5; 13C 0.8/
0.7], 254 (4), 253 (7), 252 (5), 226 (94) [27ϩ, C15H14Sϩ; 13C 16/
17, (34Sϩ13C2) 5.4/5.6], 225 (56) [C15H13Sϩ, (27ϩ- H)], 211 (30)
[C14H11Sϩ; 13C 4.6/5.0, (34Sϩ13C2) 1.7/1.7], 198 (64) [1ϩ; 13C 9/10,
(34Sϩ13C2) 3.5/3.5], 197 (21) [C13H9Sϩ], 194 (33) [C15H1ϩ4; 13C 5.5/
5.8], 193 (26) [C15H1ϩ3, 9-ethylfluorenylϩ], 179 (12) [C14H1ϩ1, 9-
0.88/0.79], 196 (100) [31aϩ; 13C 14.5/13.7; (34Sϩ13C2) 5.4/4.9], 165
(1) [C13H9ϩ], 152 (6) [C12H8ϩ; 13C 0.86/0.85]. Ϫ C28H20S2 (420.6):
calcd. C 79.96, H 4.79, S 15.25; found C 80.26, H 4.67, S 15.26.
(b) Rate of N2 Evolution from 32a: The N2 extrusion (nitrometry)
of 20 mL 0.167  32a in THF at Ϫ45 °C followed the first order;
with k1 ϭ 1.27 10Ϫ3
that of 8.
s
Ϫ1, the rate constant is 6.2 times higher than
4,4Ј-Dimethoxythiobenzophenone S-Methylide (35b)
2,2,3,3-Tetrakis(4-methoxyphenyl)-1,4-dithiane (33b). ؊ (a): The re-
methylfluorenylϩ], 178 (21) [C14Hϩ10], 165 (100) [C13H9ϩ, 9- action of thione 31b with 1 equiv. of diazomethane in THF at Ϫ78
fluorenylϩ; 13C 15/16], 152 (9) [C12H8ϩ, biphenyleneϩ], 121 (48) °C required 7 h and afforded a clear solution of 32b. Nitrometry
[C6H5ϪCϵSϩ; 13C 3.8/4.1, (34Sϩ13C2) 2.3/2.4], 77 (12) [C6H5ϩ]. Ϫ of the N2 extrusion from 20 mL of 0.15  32b in THF at Ϫ45 °C
1692
Eur. J. Org. Chem. 2000, 1685Ϫ1694

1,3-Dipolar Cycloadditions, 116
FULL PAPER
[3]
[4]
[5]
[6]
[7]
[8]
furnished k1 ϭ 3.14 10Ϫ4 sϪ1. The unstable colorless dimer 33b was
isolated. Ϫ 1H NMR: δ ϭ 2.77Ϫ3.35 (symmetric AAЈBBЈ, 5-H2/6-
H2), 3.68, 3.77 (2 s, 4 OCH3), 6.07Ϫ7.53 (m, 16 arom. H). Ϫ
C32H32O4S2 (544.7): calcd. C 70.56, H 5.92; found C 71.18, H 5.80.
E. Bergmann, M. Magat, D. Wagenberg, Ber. Dtsch. Chem.
Ges. 1930, 63, 2576Ϫ2584.
A. Schönberg, D. Cernik, W. Urban, Ber. Dtsch. Chem. Ges.
1931, 64, 2577Ϫ2581.
A. Schönberg, S. Nickel, D. Cernik, Ber. Dtsch. Chem. Ges.
1932, 65, 289Ϫ293.
Last papers: A. Schönberg, W. Knöfel, E. Frese, K. Praefcke,
Chem. Ber. 1970, 103, 938Ϫ948, 949Ϫ959.
A. Schönberg, B. König, E. Singer, Chem. Ber. 1967, 100,
767Ϫ777.
Original German text: "Leider waren alle Versuche, dem Che-
mismus der Reaktionen (3) und (4) durch Isolierung von Zwi-
schenprodukten oder auf andere Weise näher zu kommen, bis-
her erfolglos."
I. Kalwinsch, X. Li, J. Gottstein, R. Huisgen, J. Am. Chem.
Soc. 1981, 103, 7032Ϫ7033.
A personal note may be added. In a letter (1982) to the senior
author, Alexander Schönberg accepted the term "Schönberg
Reaction" and the solution of a vexing problem with pleasure.
Schönberg, a pioneer of thione chemistry, deceased in 1985 in
his 93rd year.
(b): When the same reaction was carried out in ether at Ϫ78 °C
overnight, the 2,5-dihydro-2,2-bis(4-methoxyphenyl)-1,3,4-thiadi-
azole (32b) deposited in crystals which were suction-filtered. On
warming, decomposition occurred Ͻ 0 °C.
4,4,5,5-Tetrakis(4-methoxyphenyl)-1,3-dithiolane (34a). ؊ (a): The
reaction of 2.58 g (10.0 mmol) of 31b in 50 mL of ether with ether-
eal diazomethane at room temp. required 20Ϫ30 min for the disap-
pearance of the blue color, and some drops of acetic acid removed
the yellow color of the excess of diazomethane. 34a was obtained
in colorless crystals (2.60 g, 93%), m.p. 161Ϫ162 °C (cyclohexane/
benzene); ref.[3]: 49% yield, m.p. 161Ϫ162 °C. Ϫ 1H NMR: δ ϭ
3.66 (s, 2-H2), 3.75 (s, 4 OCH3), 6.58, 7.53 (AAЈBBЈ of 16 arom.
H). Ϫ (b): Hydrogenolysis of 34a was achieved by Raney nickel in
refluxing methanol, as described above for 4. Tetrakis(4-methoxy-
phenyl)ethylene (37b) was obtained in 94% yield, m.p. 185Ϫ186.5
[9]
[10]
[11]
[12]
R. Huisgen, G. Mloston, Polish J. Chem., 1999, 73, 635Ϫ644.
DMAD is a popular choice for an active dipolarophile. It
turned out that 9 combined with thiobenzophenone 3400 times
faster than with DMAD; see R. Huisgen, X. Li, Tetrahedron
Lett. 1983, 24, 4185Ϫ4188.
J. Geittner, Ph. D. Thesis, Univ. of Munich, 1974; pp 144Ϫ145;
J. Geittner, R. Huisgen, R. Sustmann, Tetrahedron Lett. 1977,
18, 881Ϫ884.
L. Fisera, R. Huisgen, I. Kalwinsch, E. Langhals, X. Li, G.
Mloston, K. Polborn, J. Rapp, W. Sicking, R. Sustmann, Pure
Appl. Chem. 1996, 68, 789Ϫ798.
R. Huisgen, E. Langhals, Tetrahedron Lett. 1989, 30,
5369Ϫ5372.
K. N. Zelenin, V. V. Alekseev, V. A. Khrustalev, Zh. Org. Khim.
1984, 20, 169Ϫ180; Engl. Transl.: Russ. J. Org. Chem. 1984,
20, 152Ϫ162.
H. Fritz, P. Hug, H. Sauter, T. Winkler, S.-O. Lawesson, B. S.
Pedersen, S. Scheibye, Org. Magn. Res. 1981, 16, 31Ϫ43.
K. H. Mayer, D. Lauerer, Liebigs Ann. Chem. 1970, 731,
142Ϫ151. K. N. Zelenin, V. A. Khrustalev, V. V. Pinson, V. V.
Alekseev, Zh. Org. Khim. 1980, 16, 2237Ϫ2238; C.A. 1980, 94,
103 258k. D. M. Evans, D. R. Taylor, J.C.S., Chem. Commun.
1982, 188Ϫ189.
1
°C[3] after recrystallization from toluene. Ϫ H NMR: δ ϭ 3.70 (s,
4 OCH3), 6.5Ϫ7.1 (AAЈBBЈ, 16 arom. H). Ϫ C30H28O4 (452.5):
calcd. C 79.62, H 6.24; found C 79.61, H 6.27.
[13]
[14]
4,4Ј-Dichlorothiobenzophenone S-Methylide (35c)
2,2,3,3-Tetrakis(4-chlorophenyl)-1,4-dithiane (33c):[41] 1.06 (3.97
mmol) of 4,4Ј-dichlorothiobenzophenone (31c)[35,42] in 10 mL of
THF was cooled to Ϫ78 °C and stirred; 3.5 mL of 1.14  diazo-
methane in THF was added within 10 min. The color turned from
blue to light-yellow, and some colorless 32c deposited. The mixture
was removed from the cold bath and diluted with 200 mL of pent-
ane (20 °C). After the N2 evolution was finished, the solvent was
evaporated and the crystalline residue triturated with 15 mL of
methanol: 920 mg (82%) of 33c; recrystallized from CHCl3/pent-
[15]
[16]
[17]
[18]
1
ane, the m.p. was 154Ϫ156 °C (dec.). Ϫ H NMR: δ ϭ 2.84Ϫ3.30
(AAЈBBЈ, 5-H2/6-H2), 6.88Ϫ7.45 (m, 16 arom. H). Ϫ 13C NMR:
δ ϭ 31.2 (t, C-5/6), 63.1 (s, C-2/3), 125.7, 127.0, 132.9, 135.6 (4 d,
2 ϫ 8 arom. CH), 132.7, 133.4, 142.3, 143.9 (4 s, 2 ϫ 4 arom. Cq).
Ϫ MS (120 °C): m/z of most populous isotope peak (%): 562 (1)
[Mϩ], 470 (5) [C26H16Cl4ϩ; the intensities of the six isotope peaks
correspond to natural abundances], 266 (100) [31cϩ], 231 (63) [31cϩ
Ϫ Cl], 155 (33) [ClC6H4ϪCϵSϩ]. Ϫ C28H20Cl4S2 (562.4): calcd. C
59.79, H 3.58, S 11.40; found C 59.63, H 3.72, S 11.38.
[19]
G. Mloston and R. Huisgen, Tetrahedron, to be submitted.
[20] [20a]
R. Hoffmann, R. B. Woodward, J. Am. Chem. Soc. 1965,
87, 2046Ϫ2048. Ϫ [20b] R. B. Woodward, R. Hoffmann, J. Am.
Chem. Soc. 1965, 87, 395Ϫ397.
[21]
[22]
Discussion and review: R. Huisgen in 1,3-Dipolar Cycloaddi-
tion Chemistry (Ed.: A. Padwa), J. Wiley, New York, 1984, vol
1, pp 93Ϫ98.
R. Huisgen, X. Li, G. Mloston, C. Fulka, Eur. J. Org. Chem.
following paper.
[23]
[24]
X. Li, R. Huisgen, Tetrahedron Lett. 1983, 24, 4181Ϫ4184.
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We express our thanks to the Fonds der Chemischen Industrie,
Frankfurt, for the kind support of our research. I.K. thanks the
Deutsche Forschungsgemeinschaft for a stipend, X. L. and G. M.
are obliged to the Alexander von Humboldt Foundation for fellow-
ships. Our thanks are going to Dr. David S. Stephenson for the
[25]
1
[26]
[27]
[28]
computer simulation of an H NMR spectrum. We are grateful to
cand. chem. Jörg Gottstein for help in the experiments. We thank
Helmut Huber for many NMR spectra and Reinhard Seidl for the
MS. Helmut Schulz and Magdalena Schwarz took care of the ele-
mental analyses.
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Eur. J. Org. Chem. 2000, 1685Ϫ1694
1693

R. Huisgen, I. Kalvinsch, X. Li, G. Mloston
FULL PAPER
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Experiments done by cand. chem. K. Horchler, University of
Munich.
37, 4045Ϫ4060.
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R. Huisgen, Phosphorus, Sulfur, Silicon 1989, 43, 63Ϫ94.
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[38]
Received October 1, 1999
[O99551]
1694
Eur. J. Org. Chem. 2000, 1685Ϫ1694