Dichotomy of 1,3-dipolar cycloreversions in a tetrasubstituted 2,5-dihydro-1,3,4-thiadiazole

Article abstract of DOI:10.1002/hc.20263

The cycloaddition of diphenyldiazomethane (8) to 16 thiohetones at 40°C which furnishes tetrasubstituted 2,5-dihydro-1,3,4-thiadiazoles, is followed by rapid N₂ loss (see the preceding paper), with one exception: For the dihydrothiadiazole 10,

Full text of DOI:10.1002/hc.20263

Heteroatom Chemistry
Volume 17, Number 5, 2006
Dichotomy of 1,3-Dipolar Cycloreversions
in a Tetrasubstituted
2,5-Dihydro-1,3,4-thiadiazole
Elke Langhals and Rolf Huisgen
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: The cycloaddition of diphenyldia-
zomethane (8) to 16 thioketones at 40◦C which fur-
The rate of thermal extrusion of N2 from 2,5-dihydro-
nishes tetrasubstituted 2,5-dihydro-1,3,4-thiadiazoles,
is followed by rapid N2 loss (see the preceding pa-
per), with one exception: For the dihydrothiadia-
zole 10, the N2 extrusion is slower by a factor
of 4900 than its formation from 8 and 2,2,6,6-
tetramethycyclohexanethione (7). This elimination of
N2 is a 1,3-dipolar cycloreversion which affords a
thiocarbonyl ylide + N2 As a consequence of steric
hindrance in the example of 10, a concomitant sec-
ond cycloreversion furnishes thiobenzophenone (12)
and the diazocyclohexane derivative 13 in an equi-
librium. The complex kinetic system of Scheme 2
is confirmed by the irreversible interception of 13
with thioketone 14. The structural conditions for re-
tarded N2 extrusions from dihydrothiadiazoles are dis-
1,3,4-thiadiazoles (1) shows a high dependence on
the substitution pattern. The gain in bond energy
during the conversion of the cyclic azo compound
1 into the N2 molecule affords the thermodynamic
driving force, but also the substituted thiocarbonyl
ylide (2) affects the energy level of the transition state
(TS), as summarized in the preceding paper [1].
The first-order rate constant of N2 elimination
exhibits nearly the same numerical value for the
sterically hindered tetramethylcyclopentane-spiro-
compound 4 at 45◦C as for the 2,2-diphenyl deriva-
tive 5 at –45◦C (Scheme 1) [2,3]; that corresponds
to a decrease of the activation free energy by
7 kcal mol−1 as a consequence of the gain in
conjugation.
ꢀ
C
cussed. 2006 Wiley Periodicals, Inc. Heteroatom Chem
17:443–448, 2006; Published online in Wiley InterScience
(www.interscience.wiley.com). DOI 10.1002/hc.20263
1,3-Dipolar Cycloadditions, 134; for part 133 see [1] (the pre-
ceding paper). Dedicated to the memory of Gu¨ nther Ohloff, Bern,
Switzerland.
Correspondence to: Rolf Huisgen; e-mail: Rolf.Huisgen@cup.
uni-muenchen.de
Present address of Elke Langhals: Consortium fu¨r Elektro-
chemische Industrie, Wacker Chemie GmbH, Zielstattstr. 20,
D-81379 Mu¨nchen, Germany.
c
ꢀ
SCHEME 1
2006 Wiley Periodicals, Inc.
443

444 Langhals and Huisgen
The process of N2 elimination from dihydrothi-
adiazoles 1 looks deceptively simple. In this 1,3-
dipolar cycloreversion, we face the same structural
changes that characterize concerted 1,3-dipolar cy-
cloadditions and Diels–Alder reactions. The loosen-
ing of the two C N bonds is synchronized with two
90◦ rotations about the C S bonds generating the
planar thiocarbonyl ylide 2, a 1,3-dipole. The res-
onance energy of the parent thiocarbonyl ylide 2,
R = H, amounts to 19.3 kcal mol−1, as calculated
from the rotational barrier with UB3LYP/6-31G∗ [4].
Not only the gain in conjugation becomes
perceptible in the rate of nitrogen extrusion; steric
factors exerted by voluminous substituents may
decelerate the process. The cycloaddition of
diphenyldiazomethane (8) to thioketones at
40◦C furnishes tetrasubstituted 2,5-dihydro-1,3,4-
thiadiazoles 6 [1]; as a consequence of substitution
by phenyl, they eliminate N2 in a fast subsequent
cycloreversion. There was one exception among 16
studied examples: the adduct 10 resulting from 8
and 2,2,6,6-tetramethylcyclohexanethione (7) was
isolable (Scheme 2).
azole 10 was isolated (66% yield) and characterized.
In benzene solution at 50◦C, the N2 elimination of 10
became observable. After 24 h at 50◦C, the 1H NMR
analysis with weight standard indicated the tetrasub-
stituted thiirane 9 in 81% yield.
The NMR parameters confirm the structure. Five
13C doublets for aromatic CH and one singlet for
two aromatic Cq display isochronous, but rotation-
ally hindered, phenyl groups. The mass spectrum of
9 presents —besides the loss of sulfur and alkyl—the
radical anion of thiobenzophenone (m/z 198, 62%)
and 9-fluorenyl+ (m/z 165, 64%). The base peak, m/z
123, is probably C9H+15 as fragment of the tetrame-
thylcyclohexane residue.
Thus, the cycloreversion of 10 provided N2 and
the tetrasubstituted thiocarbonyl ylide 11, which en-
tered the usual electrocyclization. In kinetic mea-
surements, the N2 evolution at 50◦C obeyed the first-
order law only up to 69–74% reaction with half-lives
of 76 min in xylene and 113 min in nitrobenzene.
A modest negative influence of solvent polarity has
been observed for the N2 elimination of many 2,5-
dihydro-1,3,4-thiadiazoles [5].
The reaction solution after N2 extrusion contai-
ned a side-product: the occurrence of thiobenzophe-
none (12, 7%) suggested a concomitant cyclorever-
sion to 12 and 2,2,6,6-tetramethyldiazocyclohexane
(13). When the thermolysis of 10 (toluene, 50◦C,
19 h) was carried out in the presence of 2,2,4,4-
tetramethyl-3-thioxocyclobutanone (14, 1.1 equiva-
lent), the yield of thiobenzophenone, spectrophoto-
metrically determined, was 46%; the N2 evolution
was reduced to 51%. Thione 14 intercepted the
(not isolated) diazoalkane 13, and the new dispiro-
dihydrothiadiazole 15 as a cycloaddition product
was isolated. Analyses and NMR spectra were in ac-
cordance with structure 15. The 13C singlet at ꢀ 219.3
for C O demonstrates the intact cyclobutanone ring
which—in the mass spectrum—is responsible for the
loss of dimethylketene (m/z 252, 81%); the occur-
rence of 14+ (m/z 156, 15%) suggests some cyclore-
version, and C9H+15 (m/z 123, 65%) comes from the
tetramethylcyclohexane ring.
SEVERAL PATHWAYS OF CYCLOREVERSION
When the reactants 7 and 8 were combined in ether
at room temperature, the crystalline dihydrothiadi-
1
The H NMR analysis of the interception exper-
iment (toluene, 50◦C) denoted that two cyclorever-
sion processes, b and c in Scheme 2, participated in
the ratio 52:48; more precisely, 45% of thiirane 9 and
42% of 15 were found.
At room temperature, the cycloreversions of 10
are slow but clean. The reaction in benzene in the
presence of 1.1 equivalent of 14 was monitored by
1H NMR; after 14 days 10 was consumed, and a
39:61 ratio of thiirane 9 and interception product
15 was observed. An experiment in toluene at 4◦C
with 10 equivalents of 14 was run for 4 months, and
SCHEME 2
Heteroatom Chemistry DOI 10.1002/hc

Dichotomy of 1,3-Dipolar Cycloreversions in a Tetrasubstituted 2,5-Dihydro-1,3,4-thiadiazole 445
the product ratio was shifted further toward 15 (for
analytical difficulties, see the Experimental).
The complex kinetic system of Scheme 2 can be
described by two extremes. In the first, the equi-
librium 10 ꢀ 12 + 13 is rapidly established and the
interception by 14 is slow; here, the product ratio
9/15 should move toward 15 with increasing con-
centration of the intercepting thione 14. The second
extreme is characterized by an irreversible cyclore-
version c (i.e., k−c = 0), and 9/15 = kb/kc should be in-
dependent of the excess concentration of 14. The
following arguments speak for the first alternative
with some correction toward an intermediate rate
situation.
SCHEME 3
posedly, some thermal decomposition of diazoalkane
13 at 50◦C left an equivalent amount of 12 uncom-
bined.
6. It is an open question whether the cycloaddi-
tion 7 + 8 is likewise reversible under the reaction
conditions; path a (with k−a) would be the third cy-
cloreversion mode of 10 (Scheme 2). The two pairs,
7 + 8 and 12 + 13, probably differ in the energies of
ground state and TS.
A precedent to 10 is the dihydrothiadiazole 18
which Barton et al. prepared from two reactant pairs
in the synthetic context of very hindered olefins by
two-fold extrusion (Scheme 4) [8]. Despite phenyl
substitution, 18 was isolated and eliminated N2 in
refluxing THF.
That brings us back to the original observation
of the exceptional stability of 10 among the cy-
cloadducts of diphenyldiazomethane which lose N2
rapidly [1]. What is the rate ratio for the forma-
tion of 10 and its N2 extrusion ? Dihydrothiadiazole
4 eliminates N2 in xylene at 50◦C 3.1 times faster
than at 40◦C [9]. Assuming the same temperature
factor for the cycloreversion b of 10, measured at
50◦C in xylene, kb = 4.7 × 10−5s−1 comes out for 40◦C
(Scheme 2). The rate constant for the cycloaddition
7 + 8 → 10 at 40◦C in DMF (0.579 L mol−1s−1, [1])
is calculated for the less polar CHCl3, and the re-
sulting ka = 0.230 L mol−1s−1 is ≈4900 times faster
than the N2 extrusion of 10. In contrast, even for
the lower homolog, 6B in Scheme 5, the rate con-
stant of N2 elimination exceeds that of formation by
far.
1. The presence of thione 14 decreases the N2 vol-
ume and the yield of thiirane 9. The growing amount
of thiobenzophenone (12) indicates that the diazocy-
clohexane 13 is withdrawn from an equilibrium by
capturing with 14.
2. Thiobenzophenone (12) and the intercept-
ing thione 14—with rate constants k−c and kd in
Scheme 2—compete for tetramethyldiazocyclohex-
ane (13). With kd [14] ≥ k−c[12], the experimental
ratio, 9/15 = 39:61 (benzene, room temp.), should
correspond to kb/kc, the rate constants of the two
cycloreversions. The conversion of 10 to 12 + 13 is
rate determining, and 14 has at the beginning the
advantage of a higher concentration (1.1 equivalents
with respect to 10) in the competition for 13; the
concentration of thiobenzophenone would build up
and reach [12] = [14] = 0.55 equivalent after 90% re-
action. However, a high ratio kd/k−c is inherently im-
probable, since 12 is 2.2 times more reactive than 14
in the cycloaddition with diphenyldiazomethane (8)
[1].
3. If the reaction 12 + 13 → 10 is not completely
suppressed, the product ratio 9/15 should respond to
an increase of (14). In the experiment with 10 equiv-
alents of 14, the percentage of 15 in the product was
increased and that of 9 dropped from 39% to about
30–33% (analytical difficulties were mentioned). The
data still do not provide a definitive value of kb/kc.
4. Why is the cycloaddition 12 + 13 ꢀ 10 re-
versible whereas 13 + 14 → 15 is irreversible un-
der the reaction conditions? In contrast to the cy-
cloaliphatic thione 14, thiobenzophenone (1) loses
conjugation energy in the cycloaddition. A related
case: In the reaction with N-methyl-C-phenylnitrone
(16), thione 14 furnished the cycloadduct 17 which,
in solution, shows a minor dissociation to the reac-
tants. Due to unfavorable equilibria, thiobenzophe-
none and fluorene-9-thione do not react with nitrone
16 (Scheme 3) [6,7].
5. In the reaction without the intercepting thione
14, the blue color reveals thiobenzophenone. Sup-
SCHEME 4
Heteroatom Chemistry DOI 10.1002/hc

446 Langhals and Huisgen
STERIC HINDRANCE TO THE ELIMINATION
OF N2
Various observations in the chemistry of thiocar-
bonyl ylides 2 point to increasing steric hindrance by
R2 = tetramethylcycloalkyl in the sequence A < B < C
(Scheme 5). The TS of N2 elimination of dihydrothi-
adiazoles 6 may be more closely related to the start-
ing material than to the product, the thiocarbonyl
ylide. The unusual stability of 10 is aptly ascribed to
the steric hindrance of N2 extrusion and—to a minor
degree—to the bulk effect of substituents in 11. The
hindrance pertains to the rotations and distortions
which are required in the course of the 1,3-dipolar
cycloreversion.
A related stabilizing effect of the tetramethylcy-
clohexane residue was observed in the spirocyclic
ketene imine 19C (Scheme 5). The first-order iso-
merization of 19A affording thiolane 20 via 21 has a
half-reaction time of 8.7 h at 60◦C [10] versus 38.5 h
at 80◦C for 19C (both in C6D6) [11]; 19B is even more
labile than 19A [12].
Calculations (B3LYP/6-31G*) of thiobenzophe-
none S-methylide (20) show that the endo-phenyl is
twisted by 44◦ versus the CSC plane; the exo-phenyl
with the smaller dihedral angle (35◦) interacts some-
what more favorably with the allylanionic π system
[13]. Compared with 20, the tetramethylcyclohex-
ane residue in 11 will increase the dihedral angles
of phenyl, endo-Ph > exo-Ph, but phenyl conjugation
still lowers the TS in the formation of 11. That is
demonstrated by the stability of dihydrothiadiazole
SCHEME 6
15, the interception product, which is more stable
than 10. It is worth mentioning that calculations of
thiocarbonyl ylide 21 reveal Cs symmetry in the most
stable conformation. The strain created by the bulky
tetramethylcyclopentane ring is reflected in the an-
gle CSC which is widened from 114◦ in 22 [4] to 118◦
in 21 [14] (see Scheme 6).
A final consideration discloses the stabilizing ef-
fect of methyl as third and fourth substituents in
the dihydrothiadiazoles 1, 23, and 24 (Table 1). The
methyl group as third substituent in 23 has only a
moderate influence on the first-order rate constant
of cycloreversion in the three model systems with
R2 = A, D, B; this methyl can dodge and will wind
up as exo-methyl in the thiocarbonyl ylide. However,
the 5,5-dimethyl derivatives 24 show lower rate con-
stants of N2 extrusion by factors of 7.2, 48, and 316,
respectively. Thus, it is the fourth substituent that
creates the extra strain in the TS of N2 elimination,
increasing in the sequence A < D < B.
EXPERIMENTAL
General [1]
2,2,6,6-Tetramethylcyclohexanethione (7) and Di-
phenyldiazomethane (8). 6,6,10,10-Tetramethyl-3,3-
diphenyl-4-thia-1,2-diazaspiro[4.5]dec-1-ene
(10).
When the solutions of 7 (850 mg, 4.99 mmol) [7,15]
and 8 (970 mg, 4.99 mmol), each in diethyl ether
(5 mL), were combined at room temperature with
stirring, the precipitation of colorless needles began
after few seconds without liberation of N2. After
1 h, filtering and washing with ether furnishes 10
(1.21 g, 66%), mp 129◦C (gas evolution). IR (KBr)
ν 693 m, 698 st, 746 m, 759 m (arom. out-of-plane
deform.), 971 st, 1380 m, 1388 m; 1447 st, 1489 m,
1
1555 w, 1595 w (arom. ring vibr., N N). H NMR
(C6D6, 80 MHz) δ 0.44, 1.13 (2 s, 4 Me), 1.23–2.30
(m, 3CH2), 6.78–7.15 (m, 6 arom. H), 7.56–7.80
(m, 4 arom. H); (CDCl3) δ 0.30 (s, 2 × 2Me), 1.19
(s, 2 × 2Me), 1.38–2.10 (m, 6H), 6.94–7.35 (m, 6
arom. H), 7.43–7.68 (m, 4 arom. H). Anal. Calcd for
C23H28N2S (364.54): C, 75.78; H, 7.74; N, 7.69; S,
8.80; found: C, 76.08; H, 7.71; N, 7.87; S, 8.82.
SCHEME 5
Heteroatom Chemistry DOI 10.1002/hc

Dichotomy of 1,3-Dipolar Cycloreversions in a Tetrasubstituted 2,5-Dihydro-1,3,4-thiadiazole 447
TABLE 1 Cycloreversion of Dihydrothiadiazoles in Xylene; Kinetics of N2 Evolution Rate Constants 104k1[s−1
]
R2
Temp. (◦C)
1
23
24
k1/k24
A
D
B
B
50
50
50
6.80
4.50
3.16
6.06
3.09
3.57
0.95
0.093
7.2
48
100
398
1.26
316
and 1.04 s−1 with r2 = 0.9986. Above 69–74% reac-
tion, systematic deviations from the first-order law
were observed.
4,4,8,8- Tetramethyl-2,2-diphenyl-1-thiaspiro[2.5]-
octane (9). (a) Thiadiazoline 10 (510 mg, 1.40
mmol) was heated in benzene (10 mL) at 50◦C for
24 h. The solution turned blue, and spectrophotom-
etry at 604 nm after some hours indicated thioben-
zophenone (12, 92 μmol, 7%). Evaporation of the sol-
vent and recrystallization from methanol afforded 9
(0.20 g, 42%) as colorless needles, mp 191–192◦C. IR
(KBr) ν 694 m, 709 st, 747 m , 783 w, 1366 m, 1382 m,
Interception of 2,2,6,6-Tetramethyldiazocyclohe-
xane (13)
1,1,3,3,7,7,11,11-Octamethyl-5 -thia-12,13-diaza-
dispiro[3.1.5.2]tridecane-2-one (15). Thiadiazoline
10 (500 mg, 1.37 mmol) and 2,2,4,4-tetramethyl-3-
thioxocyclobutanone (14, 237 mg, 1.52 mmol) [16]
in abs. benzene (5.5 mL) were stirred at room tem-
perature for 11 days. By CC (silica gel) with pentane,
thiirane 9 (0.20 g, 43%) was eluted, followed by 15
(130 mg, 29%) eluted with pentane/CH2Cl2. Recrys-
tallized from pentane, the colorless 15 showed mp
165–166◦C ( N2). IR (KBr) ν 980 w, 1024 m, 1379 m,
1447 m, 1470 m, 1480 m, 1577 w; 1792 st (C O).
1H NMR (C6D6, 80 MHz) δ 0.48, 1.13, 1.18, 1.26
(4 s, 8Me), 1.1–2.4 (m, 3 CH2); (CDCl3) δ 0.53, 1.24,
1.28, 1.32 (4 s, 8 Me), 1.45–2.21 (m, 3CH2). 13C NMR
(CDCl3, 20.2 MHz) δ 18.9 (t, C-9), 19.4, 23.6, 27.6,
29.3 (4 q, 4 × 2Me), 38.8 (t, C-8/C-10), 41.0 (s, C-7/C-
11), 67.2 (s, C-1/C-3), 111.1, 127.9 (2s, C-4, C-6), 219.3
(s, C O). MS (70 eV, 60◦C), m/z (%) 322 (16) [M+], 307
(1) [M+–Me], 294 (2) [M+–N2], 279 (6) [M+–N2–Me],
252 (81) [M+–Me2C C O], 238 (18), 224 (21) [252+–
N2], 209 (8) [224+–Me], 192 (4) [224+–S], 170 (8), 156
(15) [14+], 137 (11) [C10H1+7], 123 (65) [C9H1+5], 109
(14) [C8H+13], 95 (40) [C7H1+1], 86 (53) [Me2C C S+],
81 (60) [C6H+9 ], 69 (50) [C5H9+], 55 (40) [C4H+7 ], 41
(100) [C3H+5 ]. Anal. Calcd for C18H30N2OS (322.50):
C, 67.03; H, 9.38; N, 8.69; S, 9.94; found: C, 67.14; H,
9.25; N, 8.89; S, 10.00.
1
1444 st, 1457 m, 1485 m, 1596 w. H NMR (C6D6,
200 MHz) δ 0.45, 1.46 (2 s, 4Me), 1.0–1.8 (m, 3CH2),
6.93–7.03 (m, 6 arom. H), 7.38–7.80 (m, 4 arom.
H); (CDCl3) δ 0.24, 1.55 (2 s, 4Me), 1.12–1.84 (m,
3CH2), 6.93–7.80 (m, 10 arom. H). 13C NMR (CDCl3,
20.2 MHz) δ19.2 (t, C-6), 27.0, 33.8 (2 q, 4Me), 40.1 (s,
C-4, C-8), 45.0 (t, C-5, C-7), 70.8 (s, C-3), 75.5 (s, C-2),
126.2, 126.8, 128.5, 128.8, 130.3 (5d, 5 × 2 arom. CH),
145.5 (s, 2 arom. Cq). MS (EI, 70 eV), m/z (%) 336
(45) [M+], 321 (6) [M+–Me], 304 (5) [M+–S], 293 (4)
[M+–C3H7], 251 (84) [293+–C3H6], 219 (22) [251+–S],
211 (32), 198 (62) [C13H10S+, 12+], 165 (64) [C13H9+,
fluorenyl+], 123 (100) [C9H1+5, 13C Calcd 10.0/found
9.6], 91 (27) [C7H+7 ], 81 (21), 77 (11) [Ph+]. Anal.
Calcd for C23H28S (336.52): C, 82.08; H, 8.39; S, 9.53;
found: C, 82.19; H, 8.40; S, 9.52.
(b) Quantitat. 1H NMR analysis. Thiadiazoline 10
(0.76 mmol) in C6D6 (0.5 mL) was heated in an NMR
tube at 50◦C for 16 h. Comparison of the integrals at
δ 0.45 with that of the weight standard (as-C2H2Cl4)
furnished 81% of 9.
(c) Kinetics of N2 extrusion from 10. The N2 evo-
lution from the xylene solution at 50◦C was mea-
sured volumetrically by a nitrometer. Evaluation of
28 volume readings up to 72% by kt = log (V∞)/(V∞–
V ) furnished k1 = 1.46 × 10−4 s−1 with r2 = 0.9992;
t
a second run gave k1 = 1.60 × 10−4 s−1. Two experi-
Analysis of Competing Cycloreversions of 10.
(a) Toluene, 50◦C. The suspension of 10 (365 mg,
ments in nitrobenzene at 50◦C provided 104 k1 = 1.01
Heteroatom Chemistry DOI 10.1002/hc

448 Langhals and Huisgen
1.00 mmol) in toluene (5 mL) was stirred with thione
14 (172 mg, 1.10 mmol) under argon in a 50◦C-bath
for 19 h. The spectrophotometric analysis of thioben-
zophenone (12) at λmax 604 nm (ε = 210) gave 0.455
mmol (46%). Addition of 8 (88.0 mg, 0.453 mmol) re-
moved 12 by conversion to tetraphenyl-thiirane [1].
The residual thione 14 was responsible for the now
red color of the solution. The extinction of the iso-
lated absorption band at λmax 528 (ε = 13.2) indicated
0.45 mmol of 14 (consumption of 14: 0.65 mmol).
(b) Toluene, 50◦C. When the reaction of 10 (1.00
mmol, 0.19 M) and 14 (0.21 M) was repeated with a
gas burette connected, the N2 volume was 51% after
observed 9/15 = 45:55; the amount of 15 is probably
higher. In contrast to the experiment in toluene, 52%
of 10 was still unconsumed after 4 months. The neg-
ative effect of solvent polarity on the rate of N2 elimi-
nation, observed for several dihydrothiadiazoles [5],
is not large enough to explain the big difference in
reaction progress; probably the low solubility of 10
in acetonitrile is responsible.
ACKNOWLEDGMENTS
We thank cand. chem. Ulrich Pohl for initial exper-
iments, and the Fonds der Chemischen Industrie,
Frankfurt, for support. Helmut Huber helped in the
recording of the NMR spectra, and Reinhard Seidl
contributed the mass spectra. Helmut Schulz and
Magdalena Schwarz carried out the elemental anal-
yses. They all deserve our thanks.
1
19 h at 50◦C. Quantitative H NMR analysis (sym-
C2H2Cl4) in CDCl3 disclosed thiirane 9 (45%, s at
δ 0.24) and thiadiazoline 15 (42%, s at 0.53); 9/15 =
52:48. There are no unassigned Me singlets in the
spectrum.
(c) Benzene, room temperature. The suspension
of 10 (0.250 mmol, ≈0.24 M solution) and 14 (0.275
mmol, ≈0.27 M), in C6D6 (1.0 mL) was stirred, and
10 dissolved in several hours. The reaction progress
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[14] Sustmann, R.; Sicking, W.; Huisgen, R. Eur J Org
Chem 2005, 1505–1518.
1
was monitored by H NMR (δ 0.42 for 10 + 9, 1.47
for 9, 0.48 and 1.13 for 15, 1.05 for 14); after 17 h,
23% of 10 was still present. The signals of 10 had
disappeared after 14 days, and 9/15 = 39:61 was ob-
served; no unassigned Me singlets. The ratio did not
change in further 21 days.
(d) Toluene, 4◦C. The suspension of 10 (222 mg,
0.61 mmol) and thione 14 (926 mg, 5.93 mmol) in
toluene (5 mL) was kept in a closed flask at 4◦C for
4 months (shaking now and then until solution was
homogenous); the concentrations were ≈0.11 M in
10 and 1.02 M in 14. After evaporation of the sol-
vent, the excess of 14 was removed in high vacuum.
The 1H NMR analysis in CDCl3 (signals as above) dis-
played 9/15 = 41:59, but unassigned methyl singlets
(δ1.37, 1.47; about 25% of the used 10) raised doubts;
probably some loss of N2 from 15 occurred when the
excess of 14 was distilled off at high vacuum.
(e) Acetonitrile, 4◦C. Analogous reaction of 10
(272 mg, 0.599 mmol, 0.10 M solution) and 14
(928 mg, 5.95 mmol, 1.03 M solution) in acetonitrile
1
(5 mL) for 4 months. Work-up and H NMR analy-
sis (CDCl3) furnished 10/9/15 = 52:21:26. Again, ad-
ditional Me singlets occur at δ1.36, 1.45 and smaller
ones at 1.38, 1.41. Therefore, we do not fully trust the
[15] Klages, C.-P.; Voss, J. J Chem Res 1977, S156, M1831.
[16] Elam, E. U.; Davis, H. E. J Org Chem 1967, 32,
1562–1565.
Heteroatom Chemistry DOI 10.1002/hc