Thermal rearrangements of (arylimino)diaziridines by simultaneous cascades of pericyclic reactions

Article abstract of DOI:10.1002/ejoc.200901474

(Arylimino) diaziridines rearrange in several cascade reactions at temperatures 60-100 °C. Those that possess unoccupied ortho positions yield fluorescent: 3-amino-2H-indazoles and 2-amino-1H-benzimidazoles. If both ortho positions are blocked by methyl groups, indazoles are not formed and deeply yellow 2-imino-2,3-dihydro-3aH-benzimidazoles are formed, which partly dimerize through Diels-Alder reaction or regenerate the aromatic system, by formal loss of CH₂. In addition, one of the methyl groups of 2,6-dimethylphenyl rings is involved in a [1,7] H shift affording orthoquinonoid intermediates which undergo 1,6-electrocyclization to furnish 2-amino-3,4-dihydroquinazolines. The formation of fivemembered ring heterocycles is interpreted in terms of valence isomerization by [1,3] N shift to yield elusive 1-ary 1-3iminodiaziridines as first step. These immediately experience triaza-Cope rearrangement to benzimidazole derivatives or electrocyclic opening of the N-C bond to generate conjugated azomethine imines (1,5-dipoles), followed by their 1,5electrocyclization to indazoles. First-order rate constants of the decay of (arylimino) diaziridines refer to the [1,3] N shifts as rate-determining steps. They are larger than the corresponding rate constants for alkylsubstituted iminodiaziridines.

Full text of DOI:10.1002/ejoc.200901474

FULL PAPER
DOI: 10.1002/ejoc.200901474
Thermal Rearrangements of (Arylimino)diaziridines by Simultaneous Cascades
of Pericyclic Reactions
Helmut Quast,*[a][‡] Karl-Heinz Ross,[a] and Gottfried Philipp[a]
Dedicated to Professor Frank Seela on the occasion of his 70th birthday
Keywords: Domino reactions / Nitrogen heterocycles / Diaziridines / Ring expansion / Sigmatropic rearrangement
(Arylimino)diaziridines rearrange in several cascade reac-
tions at temperatures 60–100 °C. Those that possess unoccu-
pied ortho positions yield fluorescent 3-amino-2H-indazoles
and 2-amino-1H-benzimidazoles. If both ortho positions are
blocked by methyl groups, indazoles are not formed and
deeply yellow 2-imino-2,3-dihydro-3aH-benzimidazoles are
formed, which partly dimerize through Diels–Alder reaction
or regenerate the aromatic system by formal loss of CH2. In
addition, one of the methyl groups of 2,6-dimethylphenyl
rings is involved in a [1,7] H shift affording orthoquinonoid
intermediates which undergo 1,6-electrocyclization to fur-
nish 2-amino-3,4-dihydroquinazolines. The formation of five-
membered ring heterocycles is interpreted in terms of va-
lence isomerization by [1,3] N shift to yield elusive 1-aryl-3-
iminodiaziridines as first step. These immediately experience
triaza-Cope rearrangement to benzimidazole derivatives or
electrocyclic opening of the N–C bond to generate conju-
gated azomethine imines (1,5-dipoles), followed by their 1,5-
electrocyclization to indazoles. First-order rate constants of
the decay of (arylimino)diaziridines refer to the [1,3] N shifts
as rate-determining steps. They are larger than the corre-
sponding rate constants for alkylsubstituted iminodiazirid-
ines.
ines.[6] Furthermore, alkyl-substituted iminodiaziridines
may rearrange by [1,5] H shift to afford alkylideneguanid-
ines.[3] Aryl-substituted iminodiaziridines are expected by
analogy with aryl-substituted alkylidenecyclopropanes[7] to
experience additional thermal rearrangements involving the
aryl groups. Indeed, putative ring-arylated iminodiazirid-
ines (3), which arose from 1 by 1,3-elimination besides
stable (arylimino)diaziridines 2, were so labile at room tem-
perature that only rearranged, ring-expanded products
could be detected (Scheme 1).[3] We now studied (aryl-
imino)diaziridines 2 with the views to tracing their thermal
Introduction
Since more than a decade, cascades of pericyclic reac-
tions emerge as powerful strategies for organic syntheses.[1,2]
Here we report on thermal rearrangements by simultaneous
pericyclic cascade reactions, which have the origin in com-
mon, but take different directions. Bifurcations of this type
are rare in chemistry as well as in geography. A famous
example for the latter is Isa Lake at Craig Pass, the Conti-
nental Divide in the Yellowstone National Park, Wyoming.
In the present study, the sources of the cascades are (aryl-
imino)diaziridines 2, which we have described recently.[3]
Weakness of their NN ring bonds renders iminodiazirid-
ines more prone to thermal reorganization than alkylidene-
cyclopropanes and alkylideneaziridines. Therefore, valence
isomerizations of alkyl-substituted iminodiaziridines that
exchange the nitrogen atoms of the imino groups and the
ring nitrogen atoms by [1,3] shift[4] must surmount con-
siderably lower enthalpy barriers than analogous rearrange-
ments of alkylidenecyclopropanes[5] and alkylideneazirid-
[a] Institut für Organische Chemie der Universität Würzburg,
Am Hubland, 97074 Würzburg, Germany
[‡] Current address: Hoetgerstrasse 10, 49080 Osnabrück, Ger-
many
Fax: +49-541/8141935
Scheme 1. Aryl-substituted iminodiaziridines by base-mediated 1,3-
elimination of sulfuric acid from hydroxyguanidine O-sulfonic acids
1.
E-mail: hquast@uni-osnabrueck.de
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.200901474.
2212
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2010, 2212–2217

Thermal Rearrangements of (Arylimino)diaziridines
stability and uncovering the course of thermolysis. A respectively, but the former gave strongly fluorescent 3-
number of those ring-expanded products of 3 also emerged amino-2H-indazoles 9 (Scheme 2) while the latter produced
in the present study. The results are reported here.
colorless 2-amino-3,4-dihydroquinazolines 17 besides minor
amounts of azo compounds 15 and tert-butyl isocyanide
(16) (Scheme 3). This difference warrants separate consider-
ation of 4 and 11. Since there is no evidence for the subtle
nature of individual steps, e.g., an involvement of triazatri-
methylenemethane diradicals, we disregard conceivable di-
radical intermediates and discuss each stage of the cascades
in Scheme 2 and Scheme 3 in terms of a pericyclic reac-
tion,[8] except for the hydrogen migrations 6Ǟ9 and 8Ǟ10
(Scheme 2) and the formal loss of CH2 from 14 (Scheme 3).
Thermolyses of the (arylimino)diaziridines 4 afforded
Results and Discussion
We chose 1,2-di-tert-butyl compounds 4 and 11 for the
present study to avoid ring cleavage that affords alkylidene-
guanidines by [1,5] H shifts involving secondary or primary
alkyl substituents.[3]
Solutions of 4 and 11 in inert solvents were heated at a
temperature between 60 and 100 °C, while the conversion
1
was monitored by H NMR spectroscopy. The decay of 4
and 11 followed the first-order rate law during several half- two aminoheterocycles 9 and 10 that previously had been
lifes. This was confirmed by IR spectra in the range ν = obtained, along with 4, on 1,3-elimination of sulfuric acid
˜
1500–2000 cm–1 recorded for 0.05  (path 0.1 mm) and from 1 (cf. Scheme 1). Because the arylimino compounds 4
0.005  (path 1 mm) solutions of 11c in heptane. The IR were stable under the conditions of the elimination, both 9
spectra were superimposable after partial thermal decom- and 10 were explained by rearrangements of elusive 1-aryl-
position of 11c. As shown by constant ratios, the products 3-iminodiaziridines 5.[9] Indeed, the substitution pattern of
were persistent under the reaction conditions, except for the the NN bond in the aminoindazoles 9 proved that they
2-imino-2,3-dihydro-3aH-benzimidazoles 14 (see below). stemmed from 5: Conrotatory opening of an N–C bond of
Workup involving separation by chromatography and 5 yields conjugated azomethine imines (E)- and (Z)-7, 1,5-
crystallization afforded pure products (Table 1, entries 1, dipoles of which the latter are suitable to 1,5-electrocycliza-
10, 14, 16, 17). These were identified by comparison with tion to furnish 6 while the former are not.[10] Similar conju-
known compounds (9, 10, 14b, 14c, 16, 18b, 18c, 19c)[3] and gated azomethine imines result from the addition of unsatu-
authentic samples synthesized independently (15, 17c), or rated carbenes at azo compounds and undergo 1,5-electro-
elucidated by analytical and spectroscopic methods (17b, cyclization to indazoles.[11] The mechanism depicted in
19a). The results are compiled in Table 1.
Scheme 2 explains why the two ortho methyl groups in 11
Inspection of Table 1 reveals a principal difference be- completely inhibit formation of indazole derivatives: The
tween (arylimino)diaziridines 4 that possess at least one un- required Z configuration of hypothetical 1,5-dipoles of type
occupied ortho position and their homologs 11 whose ortho 7 cannot be adopted due to excessive strain. Even the single
positions are both blocked by methyl groups. Both types ortho methyl group in 4c disfavors the indazole route (cf.
furnished benzimidazole derivatives 10 and 14, 18, 19, entries 1–7/8, 9, Table 1).
Table 1. Reaction conditions and results of the thermal rearrangements of (arylimino)diaziridines 4 and 11. Rate constants k26,27 of the
valence isomerization 26Ǟ27 are given for comparison.[4]
Entry
Cpd.
Solvent
Conc. [mol/L] Temp. [°C][a]
Duration [h] 105ϫ k [s–1][b]
Products[c]
Ratios
1
4a
C6H6
60.0
40
3.9
9a (62), 10a
94:6
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
C6H6
C6H6
C6H6
CD3CN
C6H6
CD3CN
C6H6
CD3CN
hexane
C6H6
0.7
0.7
0.6
0.6
0.6
0.6
0.7
0.8
2
0.6
0.5
0.6
0.025
0.037
0.020
1
60.0
70.0
80.0
60.0
80.0
60.0
80.0
60.0
reflux temp.
80.0
98
60.0
reflux temp.
80.0
reflux temp.
reflux temp.
60.0
4.10Ϯ0.01
13.50Ϯ0.03
40.6Ϯ0.1
3.68Ϯ0.01
99.5Ϯ0.3
11.00Ϯ0.05
164.9Ϯ0.5
19.20Ϯ0.15
9a, 10a
9a, 10a
9a, 10a
9a, 10a
9b, 10b
9b, 10b
9c, 10c
9c, 10c
93:7
92:8
93:7
93:7
77:23
69:31
25:75
21:79
4b
4c
11a
11b
90
7.5
8
15a (10), 19a (33)[d]
14b, 15b, 17b, 18b (= 10c)
14b, 15b, 17b, 18b
14b, 17b
4.43Ϯ0.01[e]
0.59Ϯ0.001[f]
4.1[g]
66:5:26:3
56:8:23:13
73:27
C6H6
CD3CN
heptane
decalin
heptane
hexane
–
14b (38), 15b (2), 17b (8), 18b (7)
11c
6
51
14c (17), 15c (2), 17c (10), 18c (8) 65:3:22:10
14c (36), 19c (13)[d]
26
26
0.12 (k26,27
)
27
27
–
80.0
1.92 (k26,27)
[a]Ϯ0.2 °C. [b] First-order rate constants of the decay of 4 and 11. [c] Isolated yields [%] are given in brackets. [d] Isolation of further
products was not attempted. [e] k11,12/k11,13 = (14b + 15b + 18b):17b, k11,12 = 3.28ϫ 10–5 s–1, k11,13 = 1.15ϫ 10–5 s–1. [f] k11,12/k11,13
=
14b:17b, k11,12 = 0.43ϫ 10–5 s–1, k11,13 = 0.16ϫ 10–5 s–1. [g] Determined by means of a calibration curve from the decay of the IR
absorption of 11c at 1798 cm–1.
Eur. J. Org. Chem. 2010, 2212–2217
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
2213

H. Quast, K.-H. Ross, G. Philipp
FULL PAPER
isomers 5 en route 4Ǟ5Ǟ8Ǟ10.[12] However, we cannot ex-
clude that a small fraction of 10 is formed by a mechanism
beginning with a [1,5] N shift 4Ǟ8.
The polarity of the solvent did not affect the ratios 9/10
(cf. entries 2/5, 6/7, and 8/9, Table 1). This indicates that
both, the electrocyclic ring-opening of 5 to afford the puta-
tive 1,5-dipoles (Z)-7 and the triaza-Cope rearrangement of
5, show a very similar solvent dependence, as expected for
pericyclic reactions.[13]
Thermolysis of ortho-disubstituted (arylimino)diazirid-
ines 11 furnished mixtures of several products (Scheme 3),
not only of two as in case of 4. Small amounts of azo com-
pounds 15 and tert-butyl isocyanide (16) arose by [2+1]-
cycloelimination of 1-aryl-3-iminodiaziridines 12,[9] which
were formed from 11 by valence isomerization. Deeply yel-
low isomers of 11 made the appearance as major compo-
nents of the mixtures. They were identical with dihydro-
3aH-benzimidazole derivatives 14, which previously had
been isolated on elimination of sulfuric acid from 1 and
rationalized by triaza-Cope rearrangement of intermediates
12.[3] Most probably, the yellow compounds 14 were gener-
ated in this way via 12 also in the present study, but a frac-
tion might have been formed by a [1,5] N shift 11Ǟ14 in-
volving one of the ring nitrogen atoms of 11.
Scheme 2. Thermal rearrangements at 60–80 °C of (arylimino)-
diaziridines 4; for reaction conditions, see Table 1.
When the thermolyses were monitored by recording UV/
Vis spectra, formation of 14 was observed, but no isosbestic
points were detected. Their absence indicated that the yel-
low compounds 14 were not persistent under the reaction
conditions. Thus, prolonged heating of concentrated solu-
tions of 11a and 11c afforded Diels–Alder dimers 19a and
19c, respectively, of the yellow compounds 14a and 14c
(Table 1, entries 10/17). On heating of more dilute solutions
of 11b and 11c for shorter periods of time (entries 11/12/
14/16), formation of aromatic benzimidazoles 18b and 18c,
respectively, was observed. Obviously, 14b and 14c slowly
lost formally CH2, probably in a radical sequence.[14] The
dimerization 14cǞ19c and the thermal degradation in boil-
ing heptane of 14b and 14c have already been described.[3]
Separation of the mixtures by chromatography uncovered
the presence of a second type of major products, which
turned out to be colorless isomers of 11. As these were miss-
ing, when the unstable 1-aryl-3-iminodiaziridines 12 were
generated from 1 by elimination at room temperature,[3] an
involvement of 12 in the formation could be excluded. Con-
sequently, the colorless isomers were attributed to a re-
arrangement of 11. Spectroscopic evidence indicated that
one of the ortho methyl groups of 11 participated in the
isomerization.
Scheme 3. Thermal rearrangements at 60–100 °C of (arylimino)-
diaziridines 11; for reaction conditions, see Table 1.
The 2-amino-3,4-dihydroquinazoline structures 17 of the
colorless isomers of 11 were established by independent
synthesis of 17c (Scheme 4; for details, see Supporting In-
The ratios 9/10 found on thermolysis of 4 resemble those formation). Toward this end, we initially explored a syn-
that were obtained from 1 in elimination experiments at thetic route to the parent compound 23, which started with
room temperature or below and attributed to rearrange- the addition of the hydrochloride of 2-aminobenzyl alcohol
ments of intermediates 5 (9a/10a 97:3 to 98:2, 9c/10c at bis(tert-butyl)carbodiimide to yield guanidine 20.
10:90).[3] Therefore, it is highly probable that the amino- Attempts at tosylation of 20 under a variety of conditions
benzimidazoles 10, thermally generated from 4, also arise gave intractable mixtures, except in the presence of triethyl-
by triaza-Cope rearrangement of the intermediate valence amine, which afforded the stable quaternary ammonium
2214
www.eurjoc.org
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2010, 2212–2217

Thermal Rearrangements of (Arylimino)diaziridines
salt 21. Dry thermolysis of 21 under high vacuum or pro- by the polarity of the solvents (Table 1, entries 2/4). As no
longed heating of its solution in acetonitrile gave 23. How- intermediates were observed during the course of the ther-
ever, low yield of the last step and expectation of further molysis experiments, the rearrangements of 4 and 11 are the
obstacles to the synthesis of homolog 17c on this route let slow steps of the reaction cascades. Provided that they begin
us resort to the cyclization of o-aminobenzylamine 25.[15] as depicted in Scheme 2 and Scheme 3, the experimental
NBS bromination of 24 gave a 1:1 mixture of the o- and p- rate constants k can be assigned to the valence isomeriza-
nitrobenzyl bromides which reacted with tert-butylamine to tions 4Ǟ5, 11Ǟ12 and the [1,7] H shift 11Ǟ13, viz., k =
afford a 1:2 mixture of the o- and p-nitrobenzyl-N-tert-but- k4,5 (entries 1–9) and k = k11,12 + k11,13 (entries 11/13). As
ylamines. Separation by crystallization of the hydrochlo- both ring nitrogen atoms, Nsyn and Nanti, of 4, 11, and 26
rides followed by hydrogenation of the o-isomer furnished can participate in the valence isomerizations, their rate con-
25. Lithiated 25 reacted with tert-butyl isocyanide dichlo- stants are sums of the rate constants for Nsyn and Nanti
ride to yield a mixture of products from which chromatog- Alkyl substituents of the aryl rings of 4 accelerate the
raphy separated 17c, which was identical with the colorless [1,3] N shift 4Ǟ5, as long as there is one unoccupied ortho
.
thermolysis product of 11c.
position (cf. entries 4/6/8 and 5/7/9). Blocking of the free
ortho position of 4c by a methyl group to furnish 11b re-
tards the valence isomerization by more than an order of
magnitude (cf. entries 8/11 and 9/13). The reason can be
detected in Figure 1: A 2,6-dimethylphenyl ring cannot
adopt a conformation that is coplanar with the diaziridine
ring and hence optimal for conjugation with the 1,3-di-
azaallyl moiety in the transition structure of the [1,3] N
shift. Nevertheless, all aryl rings of 4 and 11 accelerate the
[1,3] N shifts compared with the methyl group of 26.[4] For
example, formal exchange of the methyl group of 26 for
a phenyl ring to afford 4a lowers the enthalpy barrier by
14 kJmol–1 from ∆H‡
= 123 kJmol–1 (Scheme 5) to
26,27
∆H‡ = 109 kJmol–1 while the entropy of activation re-
4,5
mains close to zero.
Scheme 4. Syntheses of 2-amino-3,4-dihydroquinazolines.
The formation of 17 can be explained if an antarafacial
[1,7] H shift in 11 is assumed as first step.[16,17] Conforma-
tions of 11 in solution that resemble the conformation of
11c adopted in the solid state (Figure 1)[18] are perfectly
suited to this process. The resulting orthoquinonoide inter-
mediates[19] 13 undergo 1,6-electrocyclization to afford the
2-amino-3,4-dihydroquinazolines 17.
Scheme 5.
Conclusions
(Arylimino)diaziridines 4 and 11 are labile systems and
isomerize at temperatures above 60 °C in two simultaneous
cascades of pericyclic reactions, depending on the substitu-
tion pattern of the aromatic rings. If an ortho position is
unoccupied as in 4, both cascades commence with the va-
lence isomerization to unstable 1-aryl-3-iminodiaziridines 5
and continue by ring expansions of 5 to five-membered ring
heterocycles, viz., 3-amino-2H-indazoles 9 and 2-amino-
1H-benzimidazoles 10. In contrast, two ortho methyl groups
as in 11 still permit valence isomerization to 12 and subse-
quent triaza-Cope rearrangement of 12 to 3aH-benzimid-
azoles 14, but prohibit ring expansion of 12 to indazoles.
Instead, a novel cascade originates from 11 by [1,7] H shift
which involves one of the ortho methyl groups and eventu-
ally leads to aminodihydroquinazolines 17. The only fleet-
Figure 1. Conformation of (arylimino)diaziridine 11c apt to yield
13c by antarafacial [1,7] H shift (adopted from ref. 18).
Kinetic Experiments
The first-order rate constants k measured for the decay ing existence of 1-aryl-3-iminodiaziridines and the rate con-
of 4 and 11 indicate that the thermal stabilities of (aryl- stants of the decay of (arylimino)diaziridines show that aryl
imino)diaziridines are quite limited and almost unaffected groups do not increase thermal stability compared to alkyl-
Eur. J. Org. Chem. 2010, 2212–2217
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
2215

H. Quast, K.-H. Ross, G. Philipp
FULL PAPER
crystals of 17b (0.26 g, 8%, m.p. 87 °C, from petroleum ether at
low temp.). 1H NMR (60 MHz, CCl4): δ = 1.10, 1.25, 1.48 (s, 9 H),
2.28 (s, 3 H), 3.73 (br. s, 1 H), 3.87 (s, 2 H), 6.68, 6.89 (m, 1 H)
ppm. 1H NMR (60 MHz, C6D6): δ = 1.00, 1.35, 1.47 (s, 9 H), 2.57
(s, 3 H), 3.67 (br. s, 1 H), 3.87 (s, 2 H), 6.85, 7.14 (m, 1 H) ppm.
UV (ethanol) λmax [nm] (logε) = 281 (4.81), 217 (4.33). IR (Nujol):
substituted iminodiaziridines. Instead, aryl rings accelerate
the valence isomerization by [1,3] N shift and give rise to
additional pericyclic rearrangements.
ν = 3465, 1620 cm–1. EI MS (70 eV): m/z = 329 [M+]. C H N
Experimental Section
˜
21 35
3
(329.5): calcd. C 76.74, H 10.71, N 12.75; found C 76.31, H 10.59,
N 12.63.
General: Synthetic procedures for 15, 17c, and 23; NMR, IR, and
UV/Vis spectra; and conversion-vs.-time diagrams are reported in
the Supporting Information. Petroleum ether had a boiling range
of 50–70 °C.
Thermolysis of 11c: (a) A solution of 11c (2.87 g, 10 mmol) in hep-
tane (500 mL) was heated under reflux for 6 h, followed by distil-
lation of the solvent in vacuo and drying of the residue at 10–3 Torr
to afford a viscous, yellow oil consisting of 14c, 15c, 17c, and 18c
(65:3:22:10, 1H NMR). Chromatography on basic Al2O3 with pen-
tane/diethyl ether (8:1) yielded a yellow oil (1.27 g) which was sepa-
rated by chromatography on silica gel with CH2Cl2 into 15c (2.3%
by UV/Vis, yellow oil) and, by elution with CH2Cl2/triethylamine
(20:1), crude 14c. This was chromatographed again on basic Al2O3
with pentane/diethyl ether (20:1) and distilled in a molecular distil-
lation apparatus at 60–65 °C bath temp./10–3 Torr to furnish 14c as
yellow oil (0.48 g, 17%). The 1st chromatography on basic Al2O3
was continued by elution with pentane/diethyl ether (4:1) to yield
crystals (0.33 g), which were recrystallized from petroleum ether to
yield colorless crystals of 18c (0.22 g, 8%, m.p. 120.5–121.5 °C).
The 1st chromatography on basic Al2O3 was further continued by
elution with diethyl ether to yield an oil (0.53 g), which crystallized
from pentane at –20 °C to afford colorless crystals of 17c (0.29 g,
10%, m.p. 83–85.5 °C). Repeated recrystallization from petroleum
ether raised the m.p. to 87.5–88.5 °C. (b) A solution of 11c (2.87 g,
10 mmol) in hexane (10 mL) was heated under reflux for 51 h, fol-
lowed by chromatography on basic Al2O3 with pentane. The 1st
fraction (yellow oil, 1.51 g) was distilled in a molecular distillation
apparatus at 60–65 °C bath temp./10–3 Torr to furnish 14c as yellow
oil (1.04 g, 36%). The nonvolatile residue (0.38 g, 13%) was recrys-
tallized from petroleum ether to give pale yellow crystals of 19c
(m.p. 133–134.5 °C).
Thermolysis of 4a: A solution of 4a (49 mg, 0.20 mmol) in dry ben-
zene (ca. 1 mL), contained in a sealed, degassed NMR sample tube,
was heated at (60.0Ϯ0.2) °C for 40 h, while the ratios of 4a and
1
the thermolysis products 9a and 10a were monitored by H NMR
spectroscopy (9a/10a = 94:6). Evaporation of the solvent in a
stream of N2 and recrystallization of the residue from hexane af-
forded colorless needles of 9a (30.5 mg, 62%, m.p. 97–98 °C).
Thermolysis of 11a: A solution of 11a (2.73 g, 10 mmol) in hexane
(5 mL) was heated under reflux for 90 h. Crystals of 19a precipi-
tated from the cooled solution, which were isolated by filtration
and dried in vacuo: Yellow crystals (0.89 g, 33%, m.p. 164–
164.5 °C). 1H NMR (600 MHz, HH-COSY, HC-HSQC, HC-
HMBC, C6D6): δ = 0.917 (s, 3 H, 3-CH3), 1.089 (s, 3 H, 16-CH3),
1.349 (s, 3 H, 11-CH3), 1.6–1.8 (br., 18 H), 1.712, 1.744 (s, 9 H),
5
1.804 [dd, 4J(H,H) = JH,H = 1.5 Hz, 3 H, 8-CH3], 2.499 (m, 3JH,H
3
= 7.3 Hz, 1 H, 10-H), 2.546 (part of AB spectrum, JH,H = 7.3 Hz,
3
3
1 H, 2-H), 3.301 (d, JH,H = 7.0 Hz, 1 H, 1-H), 5.265 (d, JH,H
=
8.0 Hz, 1 H, 18-H), 5.497 (dq, 3JH,H = 3.6, JH,H = 1.5 Hz, 1 H, 9-
4
H), 5.899 (dd, JH,H = 8.0, 7.0 Hz, 1 H, 17-H) ppm. 13C NMR
3
(151 MHz, C6D6): δ = 16.40 (11-CH3), 17.30 (8-CH3), 21.61 (16-
CH3), 27.70 (3-CH3), 32.30, 32.47 [(CH3)3], 44.78 (HC-2), 46.73
(C-11), 47.51 (HC-1), 54.15, 54.26, 55.19, 55.46 (quat. C), 56.79
(HC-10), 69.96 (C-3), 74.39 (C-16), 132.20 (C-8), 132.23 (HC-17),
133.64 (HC-9), 134.25 (HC-18), 158.56 (C-5), 159.79 (C-14), 181.90
(C-7), 197.94 (C-12) ppm. IR (Nujol): ν = 1670 (m), 1649 (m), 1612
˜
(s) cm–1. UV (hexane): λmax [nm] (logε) = 328 (3.65), 260 (4.19).
EI MS (70 eV): m/z = 546 [M+]. C34H54N6 (546.8): calcd. C 74.68,
H 9.95, N 15.37, mol. mass 546.8; found: C 74.70, H, 9.81, N 15.36,
mol. mass 545 (osmometric in CHCl3). Chromatography of the
mother liquor on silica gel with CH2Cl2 gave a yellow oil (1st frac-
tion, 0.55 g), half of which consisted of 15a (1H NMR). The oil
was dissolved in pentane (20 mL). The solution was extracted with
aq. HCl (2 , 4ϫ 20 mL). Drying of the organic layer with K2CO3
and distillation of the solvent in vacuo yielded 15a as yellow oil
(0.20 g, 10%).
Kinetic Experiments: NMR sample tubes were carefully freed from
traces of acids, dried at 150 °C, attached to a vacuum line
(10–5 Torr), and charged with an iminodiaziridine (ca. 0.3 mmol).
Solvents were kept over a drying agent (LiAlH4 for benzene; CaH2
for acetonitrile), degassed, and transferred in vacuo into the sample
tubes, which were degassed by means freeze-pump-thaw cycles and
sealed with a torch. The NMR sample tubes were completely im-
mersed in a thermostat (Ϯ0.2 °C). Progress of the thermolyses was
monitored by 1H NMR spectra (90 MHz, relative TMS as internal
standard). Ratios of starting materials and products were deter-
mined by 6–8 integrations of tert-butyl signals in 1H NMR spectra,
recorded at expanded scale (3 Hz/cm). Peak heights were used in
rare cases, when signal separation was not sufficient for satisfactory
integration. The errors, given in Table 1 for the first-order rate con-
stants k, are statistical errors of non-linear least-squares fits.
Thermolysis of 11b: A solution of 11b (3.30 g, 10 mmol) in heptane
(400 mL) was heated under reflux for 8 h, followed by distillation of
the solvent in vacuo into a receiver cooled to –78 °C. The distillate
contained 16 (GC, comparison with an authentic sample). The resi-
due was chromatographed with CH2Cl2 on a water-cooled column,
packed with silica gel, to afford 15b as yellow oil (51 mg, 2%, UV/
Vis). Repeated distillation at room temp./2ϫ 10–5 Torr in a subli-
mation apparatus yielded a yellow oil, which crystallized to give
orange-yellow crystals of 15b (46 mg, 2%, m.p. 94 °C). Elution with
CH2Cl2/triethylamine (20:1) gave yellow, greasy crystals (2.20 g),
whose components were separated by chromatography on a water-
cooled column, packed with basic Al2O3. Elution with benzene/
chloroform (4:1) furnished yellow cubes of 14b (1st fraction, 1.25 g,
38%, m.p. 84 °C, from petroleum ether at low temp.) and colorless
crystals of 18b (2nd fraction, 0.23 g, 7%, m.p. 114 °C, from petro-
leum ether at low temp.). Elution with diethyl ether gave colorless
Supporting Information (see also the footnote on the first page of
this article): General experimental and syntheses of authentic com-
pounds (6 pages), NMR spectra (10 pages), UV/Vis spectra (1
page), IR spectra (1 page), conversion-vs.-time diagrams (2 pages).
Acknowledgments
We express our gratitude to Mrs. Elfriede Ruckdeschel and Dr.
Matthias Grüne, University of Würzburg, for taking the high-field
NMR spectra and to Dr. Gerda Lange for recording the mass spec-
2216
www.eurjoc.org
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2010, 2212–2217

Thermal Rearrangements of (Arylimino)diaziridines
Angew. Chem. 2009, 121, 3003–3007; Angew. Chem. Int. Ed.
2009, 48, 2959–2963.
[9] Rapid degenerate equilibration 5/5Ј and 12/12Ј was invoked to
rationalize the observation that a deuterium-labeled tert-butyl
group in 1 was completely scrambled in the products 9, 10 and
14, respectively.[3]
[10] a) R. Huisgen, Angew. Chem. 1980, 92, 979–1005; Angew.
Chem. Int. Ed. Engl. 1980, 19, 947–973; b) E. C. Taylor, I. J.
Turchi, Chem. Rev. 1979, 79, 181–231; c) For a recent review
on 1,5-electrocyclizations of conjugated azomethine ylides, see
T. M. V. D. Pinho e Melo, Eur. J. Org. Chem. 2006, 2873–2888.
[11] P. J. Stang, M. G. Mangum, J. Am. Chem. Soc. 1977, 99, 2597–
2601.
tra. Financial support by the Deutsche Forschungsgemeinschaft
(DFG) and the Fonds der Chemischen Industrie, Frankfurt/Main,
is gratefully acknowledged.
[1] Reviews: a) K. Neuschütz, J. Velker, R. Neier, Synthesis 1998,
227–255; b) K. C. Nicolaou, S. A. Snyder, T. Montagnon, G.
Vassilikogiannakis, Angew. Chem. 2002, 114, 1742–1773; An-
gew. Chem. Int. Ed. 2002, 41, 1668–1698; c) A. K. Miller, D.
Trauner, Synlett 2006, 2295–2316; d) S. Arns, L. Barriault,
Chem. Commun. 2007, 2211–2221; e) J. K. Lee, D. J. Tantillo,
Ann. Rep. Prog. Chem. B: Org. Chem. 2008, 104, 260–283; f)
K. C. Nicolaou, J. S. Chen, Chem. Soc. Rev. 2009, 38, 2993–
3009; g) J. Poulin, C. M. Grisé-Bard, L. Barriault, Chem. Soc.
Rev. 2009, 38, 3092–3101.
[12] For carbon analogs of this particular Cope rearrangement, see
Ref. 7.
[2] For recent work on pericyclic cascade reactions, see: a) M. W.
Lodewyk, M. J. Kurth, D. J. Tantillo, J. Org. Chem. 2009, 74,
[13] C. Reichardt, Solvents and Solvent Effects in Organic Chemis-
try, 3rd ed., Wiley-VCH, Weinheim, Germany, 2002, chapter 5.
4804–4811; b) S. E. Steinhardt, C. D. Vanderwal, J. Am. Chem. [14] The formal loss of “CH2” from 14 is reminiscent of the pyro-
Soc. 2009, 131, 7546–7547; c) Z. Elkhayat, I. Safir, M. Aquino,
M. Perez, Z. Gandara, P. Retailleau, S. Arseniyadis, Eur. J. Org.
Chem. 2009, 2687–2694; d) L. L. W. Cheung, A. K. Yudin, Org.
Lett. 2009, 11, 1281–1284; e) P. Wipf, M. A. A. Walczak, An-
gew. Chem. 2006, 118, 4278–4281; Angew. Chem. Int. Ed. 2006,
45, 4172–4175; f) S. Arns, L. Barriault, J. Org. Chem. 2006, 71,
1809–1816; g) I. Masataka, Chem. Pharm. Bull. 2006, 54, 765–
774.
lytic cleavage of the 10-methyl group from steroidal ring A 1.4-
dien-3-ones: a) L. F. Fieser, M. Fieser, Steroids, 1st ed., Rein-
hold Publishing Corp., New York, NY, 1959, p. 479; b) C. Djer-
assi, Steroid Reactions, 1st ed., Holden-Day, San Francisco,
CA, 1963, pp. 382–383.
[15] For syntheses of 2-amino-3,4-dihydroquinazolines by cycliza-
tion of (o-aminobenzyl)amines with cyanogen bromide, see: a)
F. Ishikawa, Y. Watanabe, J. Saegusa, Chem. Pharm. Bull. 1980,
28, 1357–1364; b) E. W. Baxter, K. A. Conway, L. Kennis, F.
Bischoff, M. H. Mercken, H. L. De Winter, C. H. Reynolds,
B. A. Tounge, C. Luo, M. K. Scott, Y. Huang, M. Braeken,
S. M. A. Pieters, D. J. C. Berthelot, S. Masure, W. D. Bruinzeel,
A. D. Jordan, M. H. Parker, R. E. Boyd, J. Qu, R. S. Alexan-
der, D. E. Brenneman, A. B. Beitz, J. Med. Chem. 2007, 50,
4261–4264.
[16] C. W. Spangler, Chem. Rev. 1976, 76, 187–217.
[17] For similar [1,7] H shifts in 2,6-dimethylbenzene derivatives,
see: a) R. Fusco, F. Sannicolò, Tetrahedron Lett. 1982, 23,
1829–1830; b) R. Fusco, A. Marchesini, F. Sannicolò, J.
Heterocycl. Chem. 1986, 23, 1795–1799.
[3] H. Quast, K.-H. Ross, G. Philipp, M. Hagedorn, H. Hahn, K.
Banert, Eur. J. Org. Chem. 2009, 3940–3952.
[4] H. Quast, E. Schmitt, Chem. Ber. 1970, 103, 1234–1249.
[5] a) J. P. Chesick, J. Am. Chem. Soc. 1963, 85, 2720–2723; b) For
a summary of kinetic data, see D. A. Aue, M. J. Meshishnek,
J. Am. Chem. Soc. 1977, 99, 223–231.
[6] H. Quast, W. Risler, Angew. Chem. 1973, 85, 411–412; Angew.
Chem. Int. Ed. Engl. 1973, 12, 414–415.
[7] a) J. C. Gilbert, J. R. Butler, J. Am. Chem. Soc. 1970, 92, 2168–
2169; b) M. Jones Jr., M. E. Hendrick, J. C. Gilbert, J. R. But-
ler, Tetrahedron Lett. 1970, 11, 845–848; c) J. C. Gilbert, F.
Kurzawa, J. Org. Chem. 1979, 44, 2123–2126.
[8] For recent leading references, see: a) K. N. Houk, Y. Li, J. D.
Evanseck, Angew. Chem. 1992, 104, 711–739; Angew. Chem.
Int. Ed. Engl. 1992, 31, 682–708; b) O. Wiest, D. C. Montiel,
K. N. Houk, J. Phys. Chem. A 1997, 101, 8378–8388; c) R.
Hoffmann, D. J. Tantillo, Angew. Chem. 2003, 115, 6057–6062;
Angew. Chem. Int. Ed. 2003, 42, 5877–5882; d) M. Zora, J.
Org. Chem. 2005, 70, 6018–6026; M. Mauksch, S. B. Tsogoeva,
[18] K. Peters, H. G. von Schnering, Chem. Ber. 1976, 109, 1384–
1388.
[19] S. E. Rokita (Ed.), Quinone Methides, Wiley Series of Reactive
Intermediates in Chemistry and Biology, vol. 1, 1st ed., Wiley,
Hoboken, NJ, 2009.
Received: December 17, 2009
Published Online: February 25, 2010
Eur. J. Org. Chem. 2010, 2212–2217
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
2217