1,3-Dipolar cycloadditions of diphenyldiazomethane to thioketones: Rate measurements disclose thiones to be superdipolarophiles

Article abstract of DOI:10.1002/hc.20262

1,3-Dipolar cycloadditions of diphenyldiazomethane to thioketones afford 2,5-dihydro-1,3,4-thiadiazoles 8, which rapidly lose N₂. The liberated thiocarbonyl ylides 10 furnish thiiranes 9 by electrocyclic ring closure. The rate constants, measured by spectrophotometry (DMF, 40°C) for 16 cycloaliphatic and aromatic thioketones and one cyclic trithiocarbonate, stretch over five powers of 10 with fluorene-9-thione at the top and 2,2,5,5-tetramethylcyclopentanethione at the bottom. Electron-releasing substituents decrease the cycloaddition rate of thiobenzophenone; thus, the ambiphilic diphenyldiazomethane reacts as nucleophilic partner with the electrophilic thioketone. The influence of substituents and ring size on the reactivity of cycloalkanethiones, which are sterically hindered by two gem-dimethyl groups, will be discussed. Compared with electron-deficient C=C and C≡C bonds, thiones are superdipolarophiles.

Full text of DOI:10.1002/hc.20262

Heteroatom Chemistry
Volume 17, Number 5, 2006
1,3-Dipolar Cycloadditions of
Diphenyldiazomethane to Thioketones:
Rate Measurements Disclose Thiones
to be Superdipolarophiles
Rolf Huisgen and Elke Langhals
Department Chemie und Biochemie der Ludwig-Maximilians-Universita¨t Mu¨ nchen,
Butenandtstr. 5-13, D-81377 Mu¨ nchen, Germany
Received 2 January 2006; revised 6 February 2006
INTRODUCTION
ABSTRACT: 1,3-Dipolar cycloadditions of diphenyl-
diazomethane to thioketones afford 2,5-dihydro-1,3,4-
thiadiazoles 8, which rapidly lose N2. The lib-
erated thiocarbonyl ylides 10 furnish thiiranes 9
by electrocyclic ring closure. The rate constants,
measured by spectrophotometry (DMF, 40◦C) for
16 cycloaliphatic and aromatic thioketones and
one cyclic trithiocarbonate, stretch over five pow-
ers of 10 with fluorene-9-thione at the top and
2,2,5,5-tetramethylcyclopentanethione at the bottom.
Electron-releasing substituents decrease the cycload-
dition rate of thiobenzophenone; thus, the ambiphilic
diphenyldiazomethane reacts as nucleophilic partner
with the electrophilic thioketone. The influence of
substituents and ring size on the reactivity of cy-
cloalkanethiones, which are sterically hindered by two
gem-dimethyl groups, will be discussed. Compared
with electron-deficient C C and C C bonds, thiones
The superior dipolarophilic activity of the CS dou-
ble bond has been demonstrated by the measure-
ment of cycloaddition rates with several 1,3-dipoles:
N-methyl-C-phenylnitrone [1], thiobenzophenone
S-methylide [2,3], and, in a preliminary commu-
nication, diphenyldiazomethane [4]. For the 1,3-
cycloadditions of diphenyldiazomethane, kinetic
data for an extended set of thiones and a charac-
terization of the reaction products will be discussed
here.
In the MO discussion, the major reason for
thiones to appear as “superdipolarophiles” was
found in the low HO–LU energy distance of the
CS double bond [5,6]. Thioketones are also “su-
perdienophiles” in the Diels–Alder reaction, e.g.,
fluorene-9-thione beats maleic anhydride in the ad-
ditions to 1,3-dienes [7].
The reactions of diazomethane with aliphatic
thioketones 1 furnish regioisomeric cycloadducts,
2,5-dihydro-1,3,4-thiadiazoles 2 and 4,5-dihydro-
1,2,3-thiadiazoles 4 (Scheme 1). The ratio of 2:4
shifts toward 2, when solvent polarity and temper-
ature are low and R is a voluminous substituent
[8–11]. The sterically hindered cycloaliphatic
thioketones—our main model compounds—afford
virtually only the 1,3,4-thiadiazole derivatives 2.
Nitrogen extrusion from 2, R2C = cycloalkylidene,
takes place at 40–70◦C and produces thiiranes 6
via thiocarbonyl ylides 3. The latter are a class of
ꢀ
C
are superdipolarophiles.
2006 Wiley Periodicals, Inc.
Heteroatom Chem 17:433–442, 2006; Published online
in Wiley InterScience (www.interscience.wiley.com). DOI
10.1002/hc.20262
1,3-Dipolar Cycloadditions, 133. For part 132 see Giera, H;
Huisgen, R.; Polborn, K. Eur. J Org Chem 2005, 3781–3790.
Correspondence to: Rolf Huisgen; e-mail: Rolf.Huisgen@cup.
uni-muenchen.de
Dedicated to Lubor Fisera, Slovak University of Technology,
Bratislava, on the occasion of his 60th birthday.
c
ꢀ
2006 Wiley Periodicals, Inc.
433

434 Huisgen and Langhals
Scho¨nberg et al. broadly varied the reactants:
diarylthioketones and diaryltrithiocarbonates were
reacted with diaryldiazomethanes (59 pairs) and
provided the tetrasubstituted thiiranes, as reviewed
in 1957 [20]. The intermediacy of dihydrothia-
diazoles 8 and thiocarbonyl ylides 10 was not
recognized at that time. Beyond the analogy with
the diazomethane reaction (Scheme 1), the reaction
of thiobenzophenone with diphenyldiazomethane
at −78◦C (CH2Cl2) is quoted, which led to the
precipitation of the colorless, nearly insoluble 8,
R = Ph. In a suitable solvent, e.g., methanol, N2
evolution is fast even at −78◦C, and 9, R = Ph, is the
product [21].
SCHEME 1
nucleophilic 1,3-dipoles that cannot be isolated,
since rapid electrocyclization gives rise to thiiranes
6. However, the elusive intermediates 3 are easily
intercepted by electron-poor CC multiple bonds or
C O, C N, and C S bonds as dipolarophiles; a
wealth of five-membered heterocycles is accessible
[12–14].
With R = Ph in Scheme 1, the heteroallyl anion
system of the 1,3-dipole 3 profits from phenyl con-
jugation, and the elimination of N2 from 2 requires
a lower activation energy: compound 2, R = Ph, in
THF extruded N2 at −45◦C with a half-life of 56 min
[15,16].
1,3-Dipolar cycloadditions are sensitive to steric
effects. Tetrasubstituted thiocarbonyl ylides 10 are
less inclined to undergo cycloadditions (for some ex-
ceptions cf. [22,23]). They are not planar, but assume
a twisted conformation, which may well be the first
phase of the conrotatory electrocyclization 10 → 9
(conrotation has been established by Kellogg et al.
[24]). Thus, the rate-determining step, 1 + 7 → 8, is
followed by a fast elimination of N2.
MEASUREMENT AND DISCUSSION
OF RATE CONSTANTS
Thiocarbonyl ylide 3, R = Ph, is easily intercep-
tible. The reaction of thiobenzophenone with di-
azomethane at room temperature affords 4,4,5,5-
tetraphenyl-1,3-dithiolane 5 as a 2:1 product next
to quantitatively (“Scho¨nberg reaction”) [17,18]. At
20◦C the N2 loss of 2, R = Ph, and the cycloaddition
with a second molecule of 1, R = Ph, are much faster
than the initial cycloaddition that gives rise to 2,
R = Ph [15,16].
Diazomethane exceeds diphenyldiazomethane in the
rate of cycloaddition to thioketones. Thiobenzophe-
none 1 (R = Ph) in THF at −78◦C can be titrated with
a diazomethane solution for the fading of the blue
color. The second-order reaction of 1, R = Ph, with
diphenyldiazomethane 7 proceeds at 40◦C with the
rate constant k2 = 4.05 L mol−1 s−1 (CHCl3, Table 1),
i.e., slower by orders of magnitude. Rate constants
for the cycloadditions to some olefinic CC bonds
were measured for both diazomethane (DM) and
diphenyldiazomethane (DDM) under identical con-
ditions (DMF, 40◦C): k2,DM/k2,DDM = 266 for ethyl acry-
late, 117 for 1-phenylbutadiene, and 17 for nor-
bornene [25]. The log k2,DM (DMF, 25◦C) and log
k2,DDM(DMF, 40◦C) for reactions with 16 olefinic dipo-
larophiles showed a fairly linear relation, and dia-
zomethane is the more selective species [26].
In 1920, Staudinger and Siegwart com-
bined
thiobenzophenone
1
(R = Ph)
with
diphenyldiazomethane
7
and obtained 2,2,3,3-
tetraphenylthiirane 9 (R = Ph, Scheme 2) [19].
Originally, the high solubility of diazomethane in
dimethylformamide (DMF) was responsible for the
choice of this solvent. To keep the conditions com-
parable to the rate measurements of diphenyldia-
zomethane with CC double and triple bonds—and
here with thiones—DMF at 40◦C was chosen as stan-
dard conditions.
With T and D as concentrations of thione and
diphenyldiazomethane, the integrated rate equation
SCHEME 2
Heteroatom Chemistry DOI 10.1002/hc

1,3-Dipolar Cycloadditions of Diphenyldiazomethane to Thioketones 435
of second order takes the form:
in DMF. Electron transfer was reported for TCNE in
DMF [28], and probably the DMF radical cation is
ꢀ
ꢁ
ꢂꢃ
1
T0 D0 − T0
k2t =
ln
+ 1
(1)
the active reagent. Therefore, the cycloaddition rates
of these highly electrophilic dipolarophiles were
measured in CHCl3 at 40◦C. Thiobenzophenone 1l
was measured in both solvents: the reaction with 7
in DMF was 2.5 times faster than in CHCl3 (Table 1).
Table 1 does not list the rate constants for
the cycloadditions of 7 with electron-deficient ethy-
lene and acetylene derivatives; the previous com-
parison [4] will not be repeated here. It may just
be mentioned that thiofluorenone 1p as the top
thione surpasses k2 of TCNE 113-fold, and 7 reacts
with thiobenzophenone 134 times faster than with
dimethyl acetylenedicarboxylate, a notoriously reac-
tive CC bond dipolarophile.
The rate constants of Table 1 stretch over five
powers of 10; fluorene-9-thione 1p ranks at the top
and 2,2,5,5-tetramethylcyclopentanethione 1f and
thiofenchone 1k take the lowest positions. In Fig. 1
the thiones are ordered in groups I–V to simplify
comparisons.
D0 − T0
D0
T
The rates were measured by UV–Vis spectropho-
tometry. Both reactants contribute to the measured
absorbance A according to their molar absorption
coefficients, εT and εD, at the chosen wavelength.
With A= TεT + DεD, Eq. (2) is obtained.
A − εD(D0 − T0)
T =
(2)
εT + εD
The εD of diphenyldiazomethane is larger than
that of the cycloaliphatic thiones; therefore, λmax
of the former was used. For aromatic thioketones,
εT > εD, a wavelength close to the λmax of the thione
was chosen. Rate constants k2 were evaluated by lin-
ear regression. Table 1 provides average values of two
to six independent kinetic runs and scheme 3 defines
the seventeen thiones.
Difficulties occurred when 4,5-dioxo-1,3-
dithiolane-2-thione 1r or ethenetetracarbonitrile
(TCNE) served as dipolarophiles. Since the reaction
of 7 with TCNE in CHCl3 or acetonitrile furnished
3,3-diphenylcyclopropane-1,1,2,2-tetracarbonitrile
in high yield [27], the experiment in DMF as solvent
provided rather tetraphenylethylene, benzophe-
none, and diphenylcarbinol. Kinetic measurements
showed that the color of 7 disappeared in a first-order
reaction, a decomposition of 7 catalyzed by TCNE
The superiority of aromatic thioketones in
the cycloadditions with 7 is evident. In group
I, k2 of thiobenzophenone 1l surpasses those
of cycloaliphatic thioketones about 100 fold.
Admittedly, tetramethylcyclobutanethione 1a and
adamantanethione 1j are not fully comparable with
TABLE 1 Rate Constants and Products for the Reactions of Thiocarbonyl Compounds and Diphenyldiazomethane in DMF
(*CHCl3) at 40◦C; Lit. on Thiiranes 9l–9s in Ref. [20]
Thiirane
Thione
No.
λ (nm)
used
k2
(L mol−1s−1
)
No.
m.p. ( ◦C )
% Yield a
1a
1b
1c
1d
1e
1f
1g
1h
1j
525
525
525
520
520
525
525
525
520
520
628
4.77 × 10−2
0.139
9a
9b
9c
9d
9e
9f
9g
8h
9j
68
80
116
115
116
143
215
93
93
(74)
82
(95)
83
4.66 × 10−2
1.29
1.05
2.35 × 10−3
4.83 × 10−2
0.579
92
120 (dec)b
182–184
155–157c
0.101
(82)
97
1k
1l
2.98 × 10−3
9k
9l
10.2
4.05*
1m
1n
1p
1q
1r
628
620
440
520
532
520
0.368
9m
9n
9p
9q
9r
4.41 × 10−3
450*
5.51 × 10−2
0.506
1s
66.8*
9s
a
1H NMR analysis; in parentheses isolated yield.
2,5-Dihydro-1,3,4-thiadiazole.
Diastereomer 1.
b
c
Heteroatom Chemistry DOI 10.1002/hc

436 Huisgen and Langhals
k2 fit straight lines when plotted versus σ(ρ = 4.0)
or σ+(ρ+ = 2.0). No doubt, the thioketone is the
electrophilic and diphenyldiazomethane the nucle-
ophilic partner.
In xanthione 1q (group III), the electron-
releasing o,oꢁ-oxygen function reduces the activity of
thiobenzophenone 1l 185-fold, even a greater effect
than that generated by two p-methoxy groups in 1m.
Fluorene-9-thione 1p is by a factor of 111 faster than
1l. The participation of an aromatic fluorenyl-type
carbanion in the TS of cycloaddition may lower the
barrier height. Moreover, the bathochromic shift in
the light absorption [29] demonstrates the changed
ꢀ-system of 1p, compared with Il. The planarity of
1p assists the approach of the 1,3-dipole; in 1l, the di-
hedral angle between the two phenyl planes amounts
to 69◦ (X-ray [30]) and contributes to the bulk.
Inductive electron attraction across the
four-membered ring may play
a role in the
rate modulation given by 3-substituted 2,2,4,4-
tetramethylcyclobutanethiones (group IV in Fig. 1).
The O and S function increase the electrophilicity
of the dipolarophilic C-atom in 1d and 1e by factors
of 27 and 11, respectively. Smaller is the influence
of 3-SEt in 1b; the inductive effect of two 3-SEt
functions in 1c appears to be compensated by steric
hindrance.
The two gem-dimethyl groups in the cycloalka-
nethiones impede the access of the 1,3-dipole like a
grate. The dependence on the ring size (group V) re-
sults from two effects. In the four-membered ring of
1a the dimethyl groups are bent back from the reac-
tion center, whereas in the five- and six-membered
rings of 1f–1h the bond angles reach “normality”
in two steps. This is connected with an enhance-
ment of steric hindrance at the dipolarophilic C S
bond. Superimposed is the change of conformational
strain in the conversion of an sp2-hybridized center
to a tetrahedral C-atom, as exemplified by the reduc-
tion rates of cyclic ketones with sodium borohydride:
krel = 38:1:23 for the four-, five-, and six-membered
ring, respectively [31]. The I-strain concept of Brown
et al. [32] served as interpretation for a bulk of rate
and equilibrium data [33,34], but in the application
to cycloalkyl solvolysis rates [35] some reserve is rec-
ommended [36].
Mayr et al. published rate constants for the
reactions of p-substituted benzhydryl cations with
diazoalkanes in the framework of their fruitful re-
activity correlation, log k2 = s(E + N) (review: [37]).
The bis(p-dimethylamino)benzhydryl cation reacts
with diazomethane 1.3 × 104 times faster than with
diphenyldiazomethane 7. The nucleophilicity pa-
rameter N of 7 has been determined [38], but the
electrophilicity E of thiobenzophenone is unknown.
FIGURE 1 Cycloadditions of diphenyldiazomethane with
thioketones in DMF at 40◦C; relative rate constants.
1l in steric demand. The high ranking of aromatic
thiones indicates that the additional aryl conjugation
further lowers the energy of the transition structure
(TS). It would be in harmony with the TS of a
concerted cycloaddition in which the low HO–LU en-
ergy distance, i.e., the orbital compression in the con-
jugated system of 1l, is important. The bathochromic
effect of phenyl conjugation shows up in the n→ ꢀ∗
and ꢀ → ꢀ∗ transitions [29] and is observed in the
color of dilute solutions: pink for 1a and 1j, blue-
violet for 1l.
In group II, the strong retardation by electron-
releasing substituents on the cycloaddition rate of
thiobenzophenone is shown: bis(p-methoxy) and
bis(p-dimethylamino) diminish by factors of 28 and
2300. A Hammett relation based on only three
rate constants is not very significant, but the log
Heteroatom Chemistry DOI 10.1002/hc

1,3-Dipolar Cycloadditions of Diphenyldiazomethane to Thioketones 437
The knowledge of this parameter would help to an-
swer the significant question about the nature of the
cycloaddition we are dealing with here. The concert
of bond-making and -breaking should reduce the ac-
tivation free energy of the process calculated for the
making of one bond in an initiating reaction step.
There are arguments for the concertedness of
diazoalkane cycloadditions with CC double bonds:
retention of dipolarophile configuration, >99.997%,
in the addition of diazomethane to methyl-(E)-2,3-
dimethylacrylate [39]; only small dependence of
rate on solvent polarity for additions of phenyldia-
zomethane to methyl acrylate or norbornene was
observed [25]. On the other hand, the high influ-
ence of solvent polarity on the reaction of dimethyl
diazomalonate with 1-pyrrolidinocyclopentene indi-
cated a switching from cycloaddition to azo-coupling
[40] as a consequence of the low distance of LU (1,3-
dipole) and HO (dipolarophile).
Thiiranes as Products
All thiones of Scheme 3 reacted with diphenyl-
diazomethane
7
in DMF at 40◦C and fur-
nished thiiranes—with one exception: 2,2,6,6-
tetramethylcyclohexanethione 1h afforded the
dihydro-1,2,4-thiadiazole 8h, i.e., the N2 extrusion
as the second step was slow in just this case.
The conversion 8h → 9h + N2 became measurable
at higher temperature, but—oddly enough—was
accompanied by formation of thiobenzophenone.
Competing cycloreversions of 8h were revealed,
which will be the subject of the following paper. The
reactions of 7 with aromatic thioketones 1l–1r and
the cyclic trithiocarbonate 1s gave rise to thiiranes
9l–9s, which have been described before (for lit., see
[20]); a renewed isolation was regarded dispensable.
The thiiranes 9a–9k are crystalline and were
formed in high yields. The NMR spectra not only
confirmed the structures and symmetry properties,
but also allowed an assignment of all essential 13C
parameters. Thiirane 9b harbors two stereocenters
and occurred in two diastereomers 62:38; a ꢁ-plane
is retained in each of them. The fenchane derivative
showed up in two chiral diastereoisomers (46:54).
One was isolated pure and the second was enriched.
The 13C parameters of the pure isomer display differ-
ent phenyls.
SCHEME 3
furnished thiobenzophenone+ (m/z 198, in the MS of
9g as 100% peak), accompanied by benzhydryl+ (m/z
167, small), 9-fluorenyl (m/z 165, big), and PhC S+
(m/z 121); these conversions of thiobenzophenone+
are well known [41].
EXPERIMENTAL
General
The mass spectra of thiiranes 9a–9k exhibit the
loss of sulfur, often combined with the elimination
of alkyl or—in the case of 9d—carbon monoxide.
Strong M+ peaks (up to 85%) are noteworthy. As
expected from precedents, the radical cations of 9d
and 9e lose dimethylketene and dimethylthioketene,
respectively. Surprising was a fragmentation which
IR spectra were recorded on a Perkin-Elmer FT 1000
instrument. 1H NMR spectra were taken on a Bruker
WP80 CW model, and 13C NMR on Bruker WP80
DS; signal multiplicities were determined by com-
parison of H-decoupled and off-resonance spectra.
Heteroatom Chemistry DOI 10.1002/hc

438 Huisgen and Langhals
2Me of 2Et), 1.45 (s, 4Me), 2.60(q, 3 J = 7.6 Hz, 2CH2
of 2Et). 13C NMR (CHCl3, 20.2 MHz): δ 13.8 (q, 2Me
of 2Et), 26.0 (t, 2CH2 of 2Et), 26.4 (q, 4Me), 69.8
(s, C-2/C-4), 74.4 (s, C-3), 280.8 (s, C-1). MS (130◦C)
m/z (%): 262 (0.5) [M+], 233 (80) [M+− Et], 201 (73)
[M+− EtS], 172 (61) [201+− Et], 157 (11) [172+−
Me], 139 (25), 115 (19), 105 (38), 96 (31), 91 (18), 85
(60), 81 (100), 79 (25), 71 (41), 59 (74).
The MS are EI spectra with 70 eV recorded on
Finnigan MAT 90. CC is column chromatography,
and TLC is thick-layer chromatography on 20 × 20
cm glass plates with 2 mm Merck silica gel 60 PF254
Melting points are uncorrected.
.
Materials
Diphenyldiazomethane 7 [42].
Kinetic Measurements
Dimethylformamide (DMF). The commercial
solvent was purified by distillation with benzene
and water according to the procedure described by
Bunge [43]; b.p. 40◦C/8, nD25 = 1.4267.
The UV/Vis spectrophotometer Zeiss PMQ II with
solvent compensation in the second beam and 0.1–
1.0 cm quartz cuvettes were employed. The jack-
eted cuvette chamber was thermostatted at 40.0
0.1◦C, measured in the chamber. The decrease of ab-
sorbance A versus time was continuously recorded,
and the final value, E∞, deviated from the value pre-
calculated for the excess reactant by not more than
1–2.5%. The concentrations of the reactants and the
length of the light path were adopted to the reaction
rate and to Eo ≈ 1. The ratio of the reactants was var-
ied to confirm the second order, as some examples in
Table 2 demonstrate.
Equations (1) and (2) are valid for experiments
with an excess of 7; corresponding equations with D
and T exchanged were applied for runs with an ex-
cess of thione. The evaluation of k2 was based on
15–30 pairs of E/t up to 80–90% reaction, and a
computer program was employed. Linear regression
provided k2; correlation coefficients r2 > 0.996 were
standard. Despite excellent correlation coefficients
(Table 2) for the single runs, the reproducibility was
only fair. Spreads of up to 5% were observed for
independent experiments.
New Thioketones
3-Ethylsulfanyl-2,2,4,4-tetramethylcyclobutane-
thione 1b. The corresponding ketone [44] (8.08 g,
43.4 mmol) and trimethyl orthoformate (7.6 g)
in abs. MeOH (70 mL) at 0◦C were treated with
HCl and H2S. After several days, work-up with
ice/pentane and column chromatography (silica gel,
pentane) afforded 1b (4.5 g, 51%) as red liquid, b.p.
90–95◦C/12. 13C NMR (CDCl3, 20.2 MHz): δ 15.3 (q,
Me of Et), 24.0, 28.3 (2q, 4Me), 27.3 (t, CH2 of Et),
59.5 (d, C-3), 62.5 (s, C-2/C-4), 283.9 (C-1).
3,3-Bis(ethylsulfanyl)-2,2,4,4-tetramethylcyclo-
butanethione 1c. The corresponding ketone [44]
(2.70 g, 11.0 mmol) and P4S10 (3.0 g, 9.4 mmol) were
refluxed in dry pyridine (15 mL) for 3 days. Work-
up with pentane and chromatography with silica
gel/pentane gave spectroscopically pure 1c (0.89 g,
31%). 1H NMR (CCl4, 80 MHz): δ 1.25 (t, 3 J = 7.6 Hz,
TABLE 2 Reactions of Thioketones 1 with Diphenyldiazomethane 7 in DMF at 40.0◦C; Details of Spectrophotometric Rate
Runs for Three Thioketones
mmol L−1
ε
λ (nm)
used
Evaluated
to % Reaction
Correlation
1
7
1
7
k2(L mol−1s−1
)
Coefficient r2
3-Ethylsulfanyl-2,2,4,4-tetramethylcyclobutanethione 1b
6.36
7.75
4.10
2.26
525
525
6.31
6.31
90.7
90.7
80
80
0.141
0.137
0.9999
0.9994
Adamantanethione 1j
13.98
13.98
27.96
8.16
8.16
4.08
525
525
525
4.31
4.31
4.31
90.7
90.7
90.7
90
91
84
0.103
0.104
0.0956
0.9995
0.9998
0.9998
Thiobenzophenone 1l
2.47
1.83
1.94
0.427
1.89
3.14
3.14
2.30
0.603
2.30
628
628
628
628
604
157.5
3.20
90
96
82
83
84
10.3
9.86
10.7
10.6
10.3
0.9991
0.9974
0.9997
0.9999
0.9996
157.5
157.5
157.5
210
3.20
3.20
3.20
11.4
Heteroatom Chemistry DOI 10.1002/hc

1,3-Dipolar Cycloadditions of Diphenyldiazomethane to Thioketones 439
Et), 27.9 (t, CH2 of Et), 30.3, 32.2 (2q, 4Me), 45.9 (s,
C-4/C-6), 61.5 (d, C-5), 65.7 (s, C-3), 77.9 (s, C-2). MS
(80◦C), m/z (%): 368 (46) [M+], 336 (13) [M+− S], 307
(9) [336+− Et], 282 (30), 259 (22) [336+− Ph], 252
(14) [M+− EtSC4H7], 237 (45) [252+− Me], 220 (45)
[252+− S], 205 (46) [220+− Me], 165 (25) [C13H+9 ,
fluorenyl+], 141 (23), 116 (100) [EtS+ C4H7], 91
(26) [C7H+7 ], 87 (22), 77 (14) [C6H+5 ]. Anal. calcd. for
C23H28S2 (368.59): C, 74.94; H, 7.66; S, 17.40; found:
C, 74.89; H, 7.46; S, 17.47.
Preparative Experiments: Characterization
of Thiiranes
4,4,6,6-Tetramethyl-2,2-diphenyl-1-thiaspiro[2,3]-
hexane 9a. 2,2,4,4-Tetramethylcyclobutanethione
[45] 1a (440 mg, 3.09 mmol) and 7 (590 mg,
3.04 mmol), each dissolved in DMF (5 mL), were
combined with stirring at 40◦C; decolorization
was observed after about 1 h. Water (15 mL) was
added, and the product was extracted with pentane
(2 × 10 mL). The pentane phase was washed two
˚
times with water, dried with molecular sieve (3 A),
5,5-Bis(ethylsulfanyl)-4,4,6,6-tetramethyl-2,2-
diphenyl-1-thiaspiro[2,3]hexane 9c. Recrystalliza-
tion of crude 9c (74%) from MeOH gave pure
thiirane as colorless crystals, m.p. 116◦C. IR (KBr):
ν 695 w, 706 st, 746 m, 779 m (arom. out-of-plane
deform.), 1366 m, 1379 m, 1444 st, 1472 m, 1490 m,
1599 w. 1H NMR (CDCl3, Varian XR 400S, 400
MHz): δ 0.91, 1.47 (2s, 4Me), 1.21 (t, 3 J = 7.5 Hz,
2Me of 2Et), 2.54, 2.58 (2q, 3 J = 7.5 Hz, 2CH2 of
2Et), 7.09–7.18, 7.74–7.80 (2m, 6:4, 10 arom. H).
13C NMR (CDCl3, 100 MHz, DEPT): δ 13.74, 13.84
(4Me), 25.14, 26.15 (2Me of 2Et), 26.3, 28.5 (2CH2 of
2Et), 53.1 (C-4/C-6), 69.9, 75.2, 76.5 (C-2, C-3, C-5),
127.16 (2 arom. p-CH), 127.23, 130.9 (8 aromat.
o,m-CH), 140.4 (2 arom. Cq). Anal. calcd. for C25H32S3
(428.70): C, 70.04; H, 7.52; S, 22.44; found: C, 70.15;
H, 7.46; S, 22.60.
evaporated, and left a colorless powder (870 mg).
The 1H NMR analysis with sym-tetrachloroethane as
weight standard was based on two singlets at δ 0.90
and 1.11, and indicated 93% of 9a. Recrystallization
from MeOH gave analytically pure 9a, m.p. 68◦C. IR
(KBr): ν 695 st, 752 m, 782 m (arom. out-of-plane
deform.), 1366 m, 1444 st; 1490 m, 1595 w (arom.
1
ring vibr.). H NMR (CDCl3, 80 MHz): δ 0.90, 1.11
2
(2s, 4Me), 1.69, 1.78 (AB, J = 7.0 Hz, 5-H2), 7.64–
7.85 (m, 10 arom. H). 13C NMR (CDCl3, 20.2 MHz):
δ 28.5, 32.7 (2q, 4Me), 40.7 (s, C-4/C-6), 49.7 (t, C-5),
66.5 (s, C-3), 126.9, 127.1, 130.9 (3d, 10 arom. CH),
140.3 (s, 2 arom. Cq). MS (50◦C), m/z (%): 308 (10)
[M+], 276 (58) [M+− S], 261 (19) [276+− Me], 252
(12) [M+− C4H8], 237 (22) [M+− C5H11], 233 (49)
[276+− C3H7], 220 (48) [252+− S], 219 (41), 205
(100) [237+− S], 191 (9) [205+− CH2], 178 (10), 165
(18) [C13H+9 , fluorenyl+], 155 (8), 143 (7), 129 (11),
128 (11), 105 (15) [C8H+9 ], 91 (24) [C7H+7 ], 77 (14)
[C6H+5 ]. Anal. calcd. for C21H24S (308.47): C, 81.76;
H, 7.84; S, 10.40; found: C, 81.87; H, 7.66; S, 10.37.
4,4,6,6-Tetramethyl-2,2-diphenyl-1-thiaspiro[2,3]-
hexane-5-one 9d. Thione 1d [46]. The 1H NMR
analysis was based on the singlets at δ 1.05 and 1.09:
82% of 9d, m.p. 115◦C (MeOH). IR (KBr): ν 694 w,
706 st, 750 m, 783 m, 1035 m, 1363 m, 1456 st,
1465 m, 1490 w, 1775 vst (C O). 1H NMR (CDCl3, 80
MHz): δ1.05, 1.09 (2s, 4Me), 7.14–7.35 (m, 6 arom.
H), 7.53–7.75 (m, 4 arom. H). 13C NMR (CDCl3, 20.2
MHz): δ 23.5, 25.3 (2q, 4Me), 63.7 (s, C-4/C-6), 65.3
(s, C-3), 74.1 (s, C-2), 127.4 (d, 6 arom. CH), 130.6
(d, 4 arom. CH), 139.4 (s, 2 arom. Cq), 220.4 (s, C-5).
MS (70◦C), m/z (%): 322 (77) [M+], 294 (9) [M+−
CO], 290 (10) [M+− S], 262 (100) [M+− S − CO], 247
(61) [262+− Me], 219 (90) [290+− Me2C C O − H],
198 (46) [thiobenzophenone+], 165 (33) [C13H9+,
fluorenyl+], 91 (24) [C7H7+], 77 (15) [C6H+5 ]. Anal.
calcd. for C21H22OS (322.45): C, 78.22; H, 6.88; S,
9.94; found: C, 78.41; H, 6.98; S, 9.96.
5-Ethylsulfanyl-4,4,6,6-tetramethyl-2,2-diphenyl-
1-thiaspiro[2,3]hexane 9b. Analogously, 2b (2.12
mmol) and 7 (2.06 mmol) afforded crude 9b (670
mg) as a colorless powder. The NMR spectra showed
the presence of two diastereoisomers (62:38), which
were not separated; the quantitat. 1H NMR analysis
with sym-C2H2Cl4 used the q at δ 2.40 and the s at
3.05 and resulted in 93% of 9b, m.p. 80◦C (MeOH).
IR (KBr): ν 692 m, 710 st, 743 m, 778 m (arom.
out-of-plane deform.), 1259 m, 1367 st; 1451 st,
1461 m, 1490 m, 1598 w (arom. ring vibr.). 1H NMR
(CDCl3, 80 MHz) of Isomer 1: δ 0.90, 1.19 (2s, 4Me),
3
3
1.22 (t, J = 7.2 Hz, Me of Et), 2.43 (q, J = 7.2 Hz,
CH2 of Et), 3.05 (s, 5-H), 7.13–7.37, 7.63–7.85 (2m,
10 arom. H); Isomer 2: δ 0.99, 1.04 (2s, 4Me), 1.19
4,4,6,6-Tetramethyl-2,2-diphenyl-1-thiaspiro[2,3]-
hexane-5-thione 9e. Dithione 1e (10.0 mmol) [46]
and 7 (5.61 mmol) were reacted in DMF (10 mL) for
1 h at 40◦C. Work-up with H2O (30 mL) and pentane
(100 mL) gave an organic phase from which at 0◦C
a colorless powder (20 mg) precipitated, m.p. 235–
3
(t, Me of Et), 2.40 (q, J = 7.6 Hz, CH2 of Et), 3.05
(s, 5-H). 13C NMR (CDCl3, 20.2 MHz) of Isomer 1: δ
15.3 (q, Me of Et), 23.1, 32.2 (2q, 4Me), 27.1 (t, CH2
of Et), 47.3 (s, C-4/C-6), 61.5 (d, C-5), 62.5 (s, C-3),
77.9 (s, C-2), 127.2, 130.8, 131.0 (3d, 4:4:2, 10 arom.
CH), 140.1 (s, 2 arom. Cq); Isomer 2: δ 14.9 (q, Me of
1
237◦C. The IR and H NMR spectra corresponded
Heteroatom Chemistry DOI 10.1002/hc

440 Huisgen and Langhals
with the literature description of the 1:2-product,
the diastereomeric mixture of bis-thiiranes [8]
(m.p. 235–240◦C); the MS (m/z 504, 3%) confirmed
C34H32S2. The monothiirane 9e (1.81 g, 95%) was
obtained from the mother liquor at −25◦C in large
crystals, m.p. 116–116.5◦C. IR (KBr): ν 703 st, 744 m,
778 st; 865 m, 1091 st, 1312 st, 1360 st, 1444 st,
× 2 arom. Cq). MS (110◦C), m/z (%): 370 (19) [M+],
355 (1.5) [M+− Me], 338 (4) [M+− S], 323 (4) [M+−
S−Me], 293 (1) [M+− Ph], 215 (3), 198 (1) [Ph2C S+],
172 (100) [C13H1+6, tetramethylindene+; 13C calcd.
14.5/found 15.2], 165 (18) [C13H+9 , fluorenyl+], 157
(44) [C12H+13, trimethylindenyl+], 142 (7) [C11H1+0,
dimethylindenyl+], 129 (6) [C10H+9 ], 121 (5) [Ph–
C S+], 91 (8) [C7H+7 ], 77 (4) [Ph+]. Anal. calcd. for
C26H26S (370.53): C, 84.27; H, 7.07; S, 8.65; found;
C, 84.21; H, 7.11; S, 8.63.
1
1462 m, 1492 m. H NMR (CDCl3, 80 MHz): δ 1.13,
1.16 (2s, 4Me), 7.13–7.39 (m, 6 arom. H), 7.55–7.83
(m, 4 arom. H). 13C NMR (CDCl3, 20.2 MHz): δ 27.4,
29.4 (2q, 4Me), 65.7 (s, C-3), 67.2 (s, C-4/C-6), 77.3
(s, C-2), 127.4 (d, 6 arom. CH), 130.7 (d, 4 arom.
CH), 139.5 (s, 2 arom. Cq), 194.9 (C S). MS (70◦C),
m/z (%): 338 (80) [M+], 323 (7) [M+− Me], 306 (43)
[M+− S], 291 (9) [306+− Me], 261 (6) [M+− Ph],
251 (23), 237 (25), 220 (54) [306+− Me2C C S], 210
(100) [Ph2C C S+ ?], 205 (49) [220+− Me], 165 (30)
[C13H+9 , fluorenyl+], 128 (16), 121 (10) [PhC S+], 91
(13) [C7H+7 ], 77 (12) [Ph+]. Anal. calcd. for C21H22S2
(338.52): C, 74.50; H, 6.55; S, 18.94; found: C, 74.60;
H, 6.59; S, 18.96.
3ꢁ,3ꢁ-Diphenylspiro[adamantane-2,2ꢁ-thiirane] 9j.
Adamantanethione 1j [50] (0.602 mmol) and 7 (0.619
mmol) in DMF (2 mL) were reacted at 45◦C for 1 h
and treated with H2O (5 mL). Recrystallization of
the powder from EtOH furnished 9j (165 mg, 82%),
m.p. 182–184◦C. IR (KBr): ν 693 m, 705 st, 745 st,
775 st; 1348 m, 1444 st, 1467 w, 1490 m, 1596 w.
1H NMR (CCl4, 80 MHz): δ 1.25–2.33 (m, 14 H of
C10H14), 6.95–7.28 (m, 6 arom. CH), 7.40–7.54 (m, 4
arom. CH). MS (90◦C), m/z (%): 332 (77) [M+], 300
(100) [M+− S], 255 (2) [M+− Ph], 211 (14), 198 (2)
[Ph2CS+], 167 (15) [C13H1+1, benzhydryl+], 165 (30)
[C13H+9 , fluorenyl+], 129 (5), 121 (5) [PhC S+], 91
(80) [C7H+7 ], 77 (4) [Ph+]. Anal. calcd. for C23H24S
(332.49): C, 83.08; H, 7.28; S, 9.64; found: C, 83.05;
H, 7.23; S, 9.66.
4,4,7,7-Tetramethyl-2,2-diphenyl-1-thiaspiro[2,4]-
heptane 9f. Thione 1f [47,48]. 1H NMR analysis
with the singlets at δ 0.55, 1.27, 1.61: 83% of 9f, m.p.
143◦C (MeOH). IR (KBr): ν 695 m, 708 st, 750 m, 780
m (arom. out-of-plane deform.), 1365 m, 1381 w,
1
1444 st, 1462 m, 1488 m, 1598 w. H NMR (CDCl3,
80 MHz): δ 0.55, 1.27 (2s, 4Me), 1.61 (s, 5-H2/6-H2),
7.02–7.32 (m, 6 arom. H), 7.58–7.81 (m, 4 arom. H).
13C NMR (CDCl3, 20.2 MHz): δ 29.2, 31.9 (2q, 4Me),
41.6 (m, C-5/C-6), 45.4 (s, C-4/C-7), 66.4 (s, C-3),
80.8 (s, C-2), 126.7 (d, 2 arom. p-CH), 127.1, 130.9
(2d, 8 arom. o,m-CH), 141.9 (s, 2 arom. Cq). MS
(100◦C), m/z (%): 322 (85) [M+], 307 (6) [M+−Me],
290 (9) [M+− S], 251 (42) [M+− C5H11], 219 (35)
[251+− S], 198 (100) [Ph2C S+], 167 (33) [C13H1+1,
benzhydryl+], 165 (58) [C13H9+, fluorenyl+], 123 (33)
[C9H+15], 121 (13) [Ph–C S+], 109 (64) [C8H1+3], 91
(15) [C7H+7 ], 77 (8) [C6H5+]. Anal. calcd. for C22H26S
(322.49): C, 81.93; H, 8.13; S, 9.94; found: C, 82.14;
H, 8.01; S, 9.93.
3ꢁ,3ꢁ-Diphenylspiro[fenchane-2,3ꢁ-thiirane] 9k.
(1R,4S)-Thiofenchone 1k [51,52] (2.67 mmol) and 7
(2.70 mmol) in DMF (25 mL) were reacted at 40◦C for
10 h. After work-up with H2O/pentane (30 mL each),
1
the crude product was H NMR-analyzed with sym-
C2Cl4H2: the singlets at δ 0.39 + 0.42 for diastereomer
1 and δ 0.30 + 0.58 for diastereomer 2 indicated 97%
of 9k, 1/2 = 46:54. The crude product, twice recrys-
tallized from EtOH, gave pure 9k-1, m.p. 155–157◦C.
Fractional crystallization of the mother liquor af-
forded 9k-2 (80 mg), which still contained 20% of
9k-1; m.p. 90–93◦C.
9k-1. IR (KBr): ν 692 st, 703 st, 729 m, 747 m,
779 m, 1097 m, 1375 m, 1443 st, 1462 m, 1487 m,
1592 w. 1H NMR (CDCl3, 80 MHz): δ 0.39, 0.42,
0.94 (3s, 3Me), 1.04–2.49 (m, 7H), 5.94–7.35 (m,
6 arom. H), 7.55–7.73 (m, 4 arom. H). 13C NMR
(CDCl3, 20.2 MHz): δ 20.4, 27.05, 33.83 (3q, 3Me),
26.96, 32.77, 46.6 (3t, 3CH2), 43.2, 53.7, 66.8 (3s,
3 alicycl. Cq), 50.6 (d, C-4), 126.61, 126.67, 127.3,
130.5 (4d, intensity ratio ∼2:2:4:2, two diastereotopic
Ph), 140.9, 144.0 (2s, 2 arom. Cq). MS (70◦C), m/z
(%): 334 (100) [M+], 319 (10) [M+− Me], 302 (100)
[M+− S; 13C calcd. 25.6/found 24.7], 287 (9) [302+−
Me], 259 (41) [302+ − i-Pr], 198 (24) [Ph2C S+], 167
(48) [Ph2CH+], 165 (29) [C13H9+, fluorenyl+], 121 (24)
[PhC S+], 91 (49) [C7H7+], 81 (22), 77 (10) [C6H+5 ].
2,3-Dihydro-1,1,3,3-tetramethyl-3ꢁ, 3ꢁ-diphenyl-
spiro[1H-indene-2,2ꢁ-thiirane] 9g. Thione 1g [49].
In the quantitat. 1H NMR analysis of the crude
product, the singlets at δ 0.90 and 1.63 indicate 92%
of 9g, m.p. 215◦C (MeOH). IR (KBr): δ 695 m, 714
st, 761 st br, 785 m, 1028 m, 1089 m, 1380 m, 1387
1
m, 1444 st, 1483 st, 1492 w. H NMR (CDCl3, 80
MHz): δ 0.90, 1.63 (2s, 4Me), 7.00–7.31 (m, 10 arom.
H), 7.68–7.91 (m, 4 arom. H). 13C NMR (CDCl3, 20.2
MHz): δ 29.3, 31.6 (2q, 4Me), 49.2 (s, C-1/C-3), 66.3
(s, C-2), 80.3 (s, C-3ꢁ), 121.5, 127.06, 127.24, 131.1
(4d, ratio 2:4:4:4, 14 arom. CH), 141.5, 150.0 (2s, 2
Heteroatom Chemistry DOI 10.1002/hc

1,3-Dipolar Cycloadditions of Diphenyldiazomethane to Thioketones 441
[6] Sustmann, R.; Sicking, W.; Huisgen, R. J Am Chem
Soc 2003, 125, 14425–14434.
[7] Rohr, U.; Schatz, J.; Sauer, J. Eur J Org Chem 1998,
2875–2883.
[8] Krapcho, A. P.; Rao, D. R.; Silvon, M. P.; Abegaz, B. J
Org Chem 1971, 36, 3885–3890.
Anal. calcd. for C23H26S (334.50): C, 82.58; H, 7.83;
S, 9.59; found: C, 82.29; H, 7.81; S, 9.58.
9k-2. H NMR (CDCl3): δ 0.30, 0.58, 0.93. Anal.
for C23H26S (334.50); found: C, 82.68; H, 7.80; S, 9.56.
1
[9] Krapcho, A. P.; Silvon, M. P.; Goldberg, I.; Jahngen
Jr., E. G. E. J Org Chem 1974, 39, 860–861.
[10] Mloston, G.; Huisgen, R. Tetrahedron Lett 1989, 30,
7045–7048.
Ethenetetracarbonitrile (TCNE)
and Diphenyldiazomethane
[11] Huisgen, R.; Mloston, G. Polish J Chem 1999, 73,
635–644.
[12] Huisgen, R.; Mloston, G. Tetrahedron Lett 1989, 30,
7041–7045.
[13] Mloston, G.; Huisgen, R.; Huber, H.; Stephenson, D.
S. J Het Chem 1999, 36, 959–968.
[14] Mloston, G.; Huisgen, R.; Polborn, K. Tetrahedron
1999, 55, 11475–11494.
[15] Kalwinsch, I.; Li, X.; Gottstein, J.; Huisgen, R. J Am
Chem Soc 1981, 103, 7032–7033.
[16] Huisgen, R.; Kalwinsch, I.; Li, X.; Mloston, G. Eur J
Org Chem 2000, 1685–1694.
[17] Bergmann, E.; Magat, M.; Wagenberg, D. Ber Dtsch
Chem Ges 1930, 63, 2576–2584.
[18] Scho¨nberg, A.; Cernik, D.; Urban, W. Ber Dtsch Chem
Ges 1931, 64, 2577–2581.
[19] Staudinger, H.; Siegwart, J. Helv Chim Acta 1920, 3,
833–840.
[20] Scho¨nberg, A.; Ko¨nig, B.; Singer, E. Chem Ber 1967,
100, 767–777.
[21] Huisgen, R.; Li, X., Heterocycles 1983, 20,
2363–2368.
[22] Huisgen, R.; Mloston, G.; Giera, H.; Langhals, E.;
Polborn, K.; Sustmann, R. Eur J Org Chem 2005,
1519–1531.
When rate measurements with TCNE (4.24 mmol
L−1) and 7 (2.65 mmol L−1) in DMF were evalu-
ated by Eqs. (1) and (2), no straight lines were
obtained. However, the data of this and three fur-
ther experiments fulfilled the first order in 7 up
to 86–97% reaction and r2 ≥ 0.998; 103k1 = 4.94,
4.20, 4.94, and 5.18 mol s−1 in four runs strayed
more than usual. The combined reaction solutions
were worked up with water/pentane, and separa-
tion by CC (pentane/CH2Cl2 10:2) gave the follow-
ing fractions: tetraphenylethylene (17%), m.p. 200–
212◦C (MeOH), in IR spectrum and mixed m.p.
identical with an authentic sample; benzophenone
(40%), identified by TLC comparison and by mixed
m.p. of the 2,4-dinitrophenylhydrazone, 227–230◦C;
diphenylcarbinol (29%) crystallized from petroleum
ether in colorless needles, m.p. 66.5◦C, without de-
pression in mixed m.p.
[23] Mloston, G.; Huisgen, R.; Giera, H. Tetrahedron 2002,
58, 4185–4193.
[24] Buter, J.; Wassenaar, S.; Kellogg, R. M. J Org Chem
1972, 37, 4045–4060.
[25] Geittner, J.; Huisgen, R.; Reissig, H.-U. Heterocycles
1978, 11, 109–112.
[26] Fisera, L.; Geittner, J.; Huisgen, R.; Reissig, H.-U. Het-
erocycles 1978, 10, 153–158.
[27] Geittner, J. Kinetik und Mechanismus der Cycloaddi-
tionen von Diazoalkanen, Ph.D. Thesis; University of
Munich, 1974, p. 136.
[28] Rieger, P. H.; Bernal, I.; Fraenkel, G. K. J Am Chem
Soc 1961, 83, 3918–3919.
[29] Lees, W. A.; Burawoy, A. Tetrahedron 1964, 20,
1533–1545; Fabian, J.; Mehlhorn, A. Z Chem 1967,
7, 192–194.
[30] Rindorf, G.; Carlsen, L. Acta Cryst B 1979, 35,
1179–1182.
ACKNOWLEDGMENTS
We express our thanks to Professor Heinz Langhals,
Munich, who provided the computer program for the
evaluation of the second-order rate measurements.
We are grateful to Cand. Chem. Ulrich Pohl for his
diligent and competent partaking in the kinetic mea-
surements and the preparative work. We also thank
Helmut Huber for many of the NMR recordings
and Reinhard Seidl for the mass spectra. The ele-
mental analyses were carried out by Helmut Schulz
and Magdalena Schwarz. We are deeply grateful to
the Fonds der Chemischen Industrie, Frankfurt, for
supporting our research.
[31] Brown, H. C.; Ichikawa, J. H. Tetrahedron 1957, 1,
221–230.
[32] Brown, H. C.; Fletcher, R. S.; Johannesen, R. B. J Am
Chem Soc. 1951, 73, 212–221.
[33] Sicher, J. Progr Stereochem 1962, 3, 202–263.
[34] Masson, E.; Leroux, F. Helv Chim Acta 2005, 88,
1375–1386.
[35] Brown, H. C.; Borkowsky, M. J Am Chem Soc 1952,
74, 1894–1902.
[36] Roth, M.; Schade, C.; Mayr, H. J Org Chem 1994, 59,
169–172.
[37] Mayr, H.; Kempf, B.; Ofial, A. R. Acc Chem Res 2003,
36, 66–77.
REFERENCES
[1] Huisgen, R.; Fisera, L.; Giera, H.; Sustmann, R. J Am
Chem Soc 1995, 117, 9671–9678.
[2] Huisgen, R.; Li, X. Tetrahedron Lett 1983, 24, 4185–
4188.
[3] Huisgen, R.; Li, X.; Giera, H.; Langhals, E. Helv Chim
Acta 2001, 84, 981–999.
[4] Huisgen, R.; Langhals, E. Tetrahedron Lett 1989, 30,
5369–5372.
[5] Sustmann, R.; Sicking, W.; Huisgen, R. J Am Chem
Soc 1995, 117, 9679–9685.
Heteroatom Chemistry DOI 10.1002/hc

442 Huisgen and Langhals
[38] Bug, Th.; Hartnagel, M.; Schlierf, C.; Mayr, H. Chem
Eur J 2003, 9, 4068–4076.
[39] Bihlmaier, W.; Geittner, J.; Huisgen, R.; Reissig, H.-U.
Heterocycles 1978, 10, 147–152.
[45] Huisgen, R.; Mloston, G.; Giera, H.; Langhals, E.
Tetrahedron 2002, 58, 507–519.
[46] Elam, E. U.; Davis, H. E. J Org Chem 1967, 32,
1562–1565.
[40] Huisgen, R.; Reissig, H.-U.; Huber, H.; Voss, S. Tetra-
hedron Lett 1979, 32, 2987–2990.
[41] Schumann, D.; Frese, E.; Scho¨nberg, A. Chem Ber
1969, 102, 3192–3204.
[47] Klages, C.-P.; Voss, J. J Chem Res 1977, S146, M1828–
1845.
[48] Giera, H.; Huisgen, R.; Langhals, E.; Polborn, K. Helv
Chim Acta 2002, 85, 1523–1545.
[42] Miller, J. B. J Org Chem 1959, 24, 560–561.
[43] Bunge, W. Reinigung von Lo¨sungsmitteln; In
Houben-Weyl, Methoden der Organischen Chemie, 4.
Aufl., Vol. I/2; Thieme: Stuttgart, 1959; pp. 831–832.
[44] Paquer, D.; Reffet, D.; Vazeux, M. Rec Trav Chim Pays-
Bas 1978, 97, 284–288.
[49] Klages, C. P.; Voss, J. Chem Ber 1980, 113,
2255–2277.
[50] Greidanus, J. W. Can J Chem 1970, 48, 3530–3536.
[51] Sen, D. C. J Ind Chem Soc 1935, 12, 647–650.
[52] Huisgen, R.; Mloston, G.; Pro¨bstl, A. Heteroatom
Chem 2001, 12, 136–145.
Heteroatom Chemistry DOI 10.1002/hc