Report on an unusual cascade reaction between azulenes and 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (=4,5-dichloro-3,6-dioxocyclohexa-1,4- diene-1,2-dicarbonitrile; DDQ)

Article abstract of DOI:10.1002/hlca.201000031

The oxidation of 1-(3,8-dimethylazulen-1-yl)alkan-1-ones 1 with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (=4,5-dichloro-3,6-dioxocyclohexa-1,4- diene-1,2-dicarbonitrile; DDQ) in acetone/H₂O mixtures at room temperature does not only lead to the corresponding azulene-1-carboxaldehydes 2 but also, in small amounts, to three further products (Tables 1 and 2). The structures of the additional products 3-5 were solved spectroscopically, and that of 3a also by an X-ray crystal-structure analysis (Fig. 1). It is demonstrated that the bis(azulenylmethyl)-substituted DDQ derivatives 5 yield on methanolysis or hydrolysis precursors, which in a cascade of reactions rearrange under loss of HCl into the pentacyclic compounds 3 (Schemes 4 and 7). The found 1,1′-[carbonylbis(8-methylazulene-3,1-diyl)]bis[ethanones] 4 are the result of further oxidation of the azulene-1-carboxaldehydes 2 to the corresponding azulene-1-carboxylic acids (Schemes 9 and 10).

Full text of DOI:10.1002/hlca.201000031

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Report on an Unusual Cascade Reaction between Azulenes and 2,3-Dichloro-
5,6-dicyano-1,4-benzoquinone (¼4,5-Dichloro-3,6-dioxocyclohexa-1,4-diene-
1,2-dicarbonitrile; DDQ)
by Rolf Sigrist and Hans-Jꢀrgen Hansen*
Organisch-chemisches Institut der Universitꢀt Zꢁrich, Winterthurerstrasse 190, CH-8057 Zꢁrich
(phone: þ 41-44-6354231; fax: þ 41-44-6359812; e-mail: H.-J.H@access.uzh.ch)
The oxidation of 1-(3,8-dimethylazulen-1-yl)alkan-1-ones 1 with 2,3-dichloro-5,6-dicyano-1,4-
benzoquinone (¼4,5-dichloro-3,6-dioxocyclohexa-1,4-diene-1,2-dicarbonitrile; DDQ) in acetone/H2O
mixtures at room temperature does not only lead to the corresponding azulene-1-carboxaldehydes 2 but
also, in small amounts, to three further products (Tables 1 and 2). The structures of the additional
products 3 – 5 were solved spectroscopically, and that of 3a also by an X-ray crystal-structure analysis
(Fig. 1). It is demonstrated that the bis(azulenylmethyl)-substituted DDQ derivatives 5 yield on
methanolysis or hydrolysis precursors, which in a cascade of reactions rearrange under loss of HCl into
the pentacyclic compounds 3 (Schemes 4 and 7). The found 1,1’-[carbonylbis(8-methylazulene-3,1-
diyl)]bis[ethanones] 4 are the result of further oxidation of the azulene-1-carboxaldehydes 2 to the
corresponding azulene-1-carboxylic acids (Schemes 9 and 10).
1. Introduction. – More then ten years ago, we applied a procedure of Okajima and
Kurokawa [1], just published at that time, to the smooth oxidation of the Me group of
1-(3-methylazulen-1-yl)alkan-1-ones with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone
(¼4,5-dichloro-3,6-dioxocyclohexa-1,4-diene-1,2-dicarbonitrile; DDQ) in aqueous
acetone to yield the corresponding azulenecarboxaldehydes. The authors reported
for the oxidation of 3-acetylguaiazulene (¼1-(5-isopropyl-3,8-dimethylazulen-1-yl)-
ethanone; 1a) an attractive yield of 91% for carboxaldehyde 2a (Scheme 1). In our
hands, the reaction gave, in a ten times higher concentration of the reactants, also 2a as
the main product, however, in yields ranging from 40 to 60%; and to our surprise, on
TLC beside the dark red spot of 2a, at least two additional faint spots were present, a
blue one, moving distinctly faster, and a red one, moving clearly slower than 2a, which
stood for two additional products of unknown structure and in estimated yields of ca.
Scheme 1
ꢂ 2010 Verlag Helvetica Chimica Acta AG, Zꢁrich

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Helvetica Chimica Acta – Vol. 93 (2010)
5% or below. In the following part, we report on the elucidation of the structure of
these new products and speculations about the mechanisms of their formation.
2. Oxidation of 1-(3-Methylazulen-1-yl)alkan-1-ones with DDQ in Aqueous
Acetone1). – 2.1. Reactions of 1-(5-Isopropyl-3,8-dimethylazulen-1-yl)alkan-1-ones
(¼ 3-Acylguaiazulenes). In a number of oxidation experiments with DDQ and 3-
acetylguaiazulene (1a) we got, after laborious chromatographic separations, consoli-
dated yields of 5 and 6% of pure material of the unknown blue component X(1) and
the unknown brick-red component X(2), respectively. Moreover, we found a third,
relatively unstable, purple compound X(3) in an average yield of 3% (Scheme 2).
Scheme 2
The UV/VIS spectrum (CH2Cl2) of X(1) with the azulene band at 586 nm, flanked
by shoulders at 550, 618, and 686 nm, confirmed the azulene nature of the compound.
The IR spectrum (CHCl3) showed a weak band at 2222 cmꢀ1, indicating the presence of
at least one CN group in conjugation with a p-system, and a very strong absorption at
1792 cmꢀ1 only compatible, in principle, with a C¼O group as part of a strained ring
system, possibly a g-lactone, but not at all with a benzoquinone ring system, which
absorbs at frequencies more than 100 cmꢀ1 lower and shows normally two bands. Most
informative was the mass spectrum of X(1), which showed the molecular mass at m/z
432 and 430 (EI mode) and 433 and 431 (CI mode), respectively, and in both cases in a
peak ratio of 1:3, a fact that allowed us to formulate the mass balance as follows:
1a þ DDQ ¼ X(1) þ HCl
Further information on the structure of X(1) came from the NMR spectra. The
1H-NMR spectrum (CDCl3) of X(1) was very similar to that of the starting material 1a
with the exception that one of the three ss of the Me groups, namely the s for MeꢀC(8)
of 1a, was missing. Instead of this signal appeared in the spectrum of X(1) signals of a
CH2 group as AB system at d 4.10 and 3.90 with J(A,B) ¼ 16.6 Hz. Since only HB at d
3.90 showed a strong reciprocal 1H-NOE effect with the neighbored azulene H-atom at
d 7.24, we concluded that the structure of X(1) must be rigid and that it must contain
elements of chirality. The 13C-NMR spectrum (CDCl3) revealed undoubtedly the
presence of two CN groups with signals at d 115.3 and 113.1 – in a shift range quite
typical for CN groups. Most informative were HMBC measurements since they
indicated a structural neighborhood of the CH2 group and the CN group whose signal
appeared at d 115.3. Moreover, this CN group showed also a long-range coupling with
1
)
See Exper. Part for the acylation of the corresponding azulenes.

Helvetica Chimica Acta – Vol. 93 (2010)
1547
the Me signal, which appeared in the 1H-NMR spectrum as a sharp s at d 2.10 and could
be identified as the former Me group of MeCOꢀC(1) of 1a, since it was not related
with the H-atoms of the azulene ring. The second CN group at d 113.1 was also related
with the Me group at d 2.10 by long-range coupling. This fact indicated that the two CN
groups were still located at neighbored C-atoms of X(1). On the other hand, most
confusing was the observation that three 13C-signals of X(1) were located in the region
above d 160, where normally C¼O resonances are found, and only one of these signals
at lowest field (d 164.5) showed a coupling relation with the Me group at d 2.10.
Since all further structure elucidation would have been based on assumptions
without final certainty, we prepared suitable crystals of X(1) for an X-ray crystal-
structure determination, which disclosed the full structure as (6aRS,13bSR)-3-chloro-
10-isopropyl-5,12-dimethyl-2-oxo-2H-cyclohept[1,7]indeno[4,5-c]furo[3,2-b]pyran-6,6a-
(7H)-dicarbonitrile (3a).
The X-ray structure of 3a (Fig. 1) indicated a rupture of the benzoquinone moiety
of DDQ in the course of its reaction with 1a, whereby the Me group of the Ac residue of
1a re-appeared as MeꢀC(5) of the new pentacyclus. This in turn would mean that C(5)
must then be the former C¼O C-atom of the Ac group of 1a. To clarify undoubtedly
the Ac migration in the course of the formation of 3a, we synthesized 1a with a doubly
13C-labeled Ac group, i.e., 1a*, and subjected it to oxidation with DDQ. The result was
unambiguous (Scheme 3). It was indeed C(5) and its Me substituent that carried in 3a*
the double 13C-label.
Fig. 1. Stereoscopic view of the X-ray crystal structure of 3a (50% probability ellipsoids)

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Helvetica Chimica Acta – Vol. 93 (2010)
Scheme 3
The structure elucidation of X(2) was much easier. It showed in the IR spectrum
(CHCl3) a broad and strong C¼O absorption band at 1652 cmꢀ1 (1659 cmꢀ1 (KBr)),
slightly different in position in comparison with 2a (1649 cmꢀ1 (CHCl3)). On the other
1
hand, the H-NMR spectrum (CDCl3) was almost identical with that of 2a, however,
the 13C-NMR spectra (CDCl3) of 2a and X(2) revealed a characteristic difference in
the C¼O region. In contrast to 2a, where the signal showed up at d 196.3, the spectrum
of X(2) revealed two signals, one at d 196.9, close to the position of that of 2a, and the
other at d 189.0, and both C¼O signals in a ratio of intensity of ca. 2 :1. Compound X(2)
could therefore only represent 1,1’-[carbonylbis(5-isopropyl-8-methylazulene-3,1-
diyl)]bis[ethanone] (4a). This structural assignment was fully confirmed by the mass
spectrum (EI) of 4a, which exhibited the peak of the molecular mass at m/z 478, with
prominent fragment ions at m/z 463 ([M ꢀ Me]þ) and 435 ([M ꢀ Ac]þ).
The third unknown, X(3), appeared intermediately in the reaction of 1a and DDQ
and later on, with the progress of the reaction, it vanished again. So it needed some
experiments to optimize its actual amount and isolate it at this point in a maximum
yield of 3%. The IR spectrum (CHCl3) was of interest because we observed three C¼O
absorption bands at 1707, 1649, and 1625 cmꢀ1. These observations spoke for a chemical
interaction of 1a and DDQ, whereby essential parts of the quinone skeleton with ˜nC¼O
at 1649 and 1625 cmꢀ1 were still present. Indeed, the mass spectrum (ESI; MeOH/
CH2Cl2 1:1, NaI) of X(3) showed m/z at 727 and 729 for [M þ Na]þ2), in agreement
with the addition of two residues of 1a to DDQ. Last certainty brought the full analysis
1
of the H- and 13C-NMR spectra of X(3) with the unambiguous assignment of the
A detailed analysis of the [M þ Na]þ region revealed that it reflected a superposition of two
molecular ions in a ratio of ca. 1:1, namely that of [5a þ Na]þ and that of [(5a þ 2 H) þ Na]þ, due to
partial hydrogenation of 5a under the ESI conditions.
2
)

Helvetica Chimica Acta – Vol. 93 (2010)
1549
position of all atoms. The compound was identified as (1RS,2RS)-1-[(3-acetyl-7-
isopropyl-4-methylazulen-1-yl)methyl]-2-[(3-acetyl-7-isopropyl-1-methylazulen-4-yl)-
methyl]-4,5-dichloro-3,6-dioxocyclohex-4-ene-1,2-dicarbonitrile (5a).
The CH2 groups at C(1) and C(2) of 5a appear in the 1H-NMR spectrum (CD2Cl2)
as two AB systems at d 4.08 and 3.79 and d 5.10 and 4.34, respectively, with J(A,B) ¼
1
15.1 and 13.9 Hz, respectively. Since we observed no H-NOE between the two AB
systems, we assigned the trans-configuration to 5a. This view is supported by AM1
calculations of the two possible conformations of trans- and cis-1-[(3-acetyl-4,7-
dimethylazulen-1-yl)methyl]-2-[(3-acetyl-1,7-dimethylazulen-4-yl)methyl]cyclohex-4-
ene-1,2-dicarbonitrile, where the i-Pr groups of 5a were substituted by Me groups on
grounds of simplicity. The trans-form with both azulenylmethyl substituents in axial
positions (DHf8 ¼ 104.7 kcal molꢀ1) displays shortest distances of the H-atoms of the
two CH2 groups of 4.4 ꢃ, in other words, beyond the distances of measurable 1H-NOE
effects (Fig. 2). Its conformer with the azulenylmethyl substituents in diequatorial
orientations (DHf8 ¼ 107.8 kcal molꢀ1) as well as the two conformations of the cis-form
(DHf8 ¼ 102.1 and 107.8 kcal molꢀ1 for the 1-ax,2-eq and 1-eq,2-ax conformation, resp.)
show shortest H distances of 2.3 ꢃ each, i.e., well in the range of observable 1H-NOE
effects.
1
Further interesting information came from an attempt to record the H-NMR
spectrum of 5a in CD3OD. Compound 5a underwent in this solvent at room
temperature a clean reaction to 3a without any incorporation of D and to 1-[5-
isopropyl-3-([2H3]methoxymethyl)-8-methylazulen-1-yl]ethanone (6) (Scheme 4). The
same reaction was observed in MeOH, resulting in 3a and the protio form of 6.
The 13C-experiment had demonstrated that, in the course of the formation of 3a
from 1a, a migration of the Ac group under abolition of the structural integrity of the
quinone system of DDQ takes place. Therefore, we were interested in changing the Ac
group with other acyl residues and subject these modified compounds to the treatment
with DDQ. The results are summarized in Table 1. The product pattern is principally
not changed. The pivaloyl-substituted azulene 1d yielded, beside 2d, still a distinctly
larger amount of triketone 4d, and also the 1,4-diketone 5d could be isolated. However,
there was no indication for the formation of pentacyclic 3d. The oxidation of the
benzoylated azulene 1e gave only the corresponding aldehyde 2e and an increasing

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Fig. 2. Stereoscopic view of the AM1-calculated structure of 5a
Scheme 4
amount of triketone 4e but neither 3e nor 5e. The latter two experiments illustrate that
most probably steric and electronic factors of the acyl group play a decisive role in the
formation of the cascade products 3.
2.2. Reactions of 1-(5-Alkyl-3,8-dimethylazulen-1-yl)ethanones. In a further series
of experiments, we tested a possible steric influence of the i-Pr group at C(5) of 1a on
product formation. The results are listed in Table 2 together with those of our standard
compound 1a. They clearly indicate that a substituent at C(5) of 1 has no influence on
the product pattern.
For the formation of the bis-azulenylated products 5, which easily rearrange to the
pentacycles 3 (Scheme 4), it is obligatory that the 1-(azulene-1-yl)alkan-1-ones 1,
subjected to the oxidation with DDQ, carry Me groups at C(8) and C(3). On the other
hand, the structure of the pentacycles 3 shows only MeꢀC(8) engaged in the
construction of the pentacycles. For this reason, we subjected also the 3-unsubstituted
azulene 1j, readily available by decarbonylation of 2a with Wilkinsonꢄs catalyst, to the

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1551
Table 1. Oxidation of 1-(5-Isopropyl-3,8-dimethylazulen-1-yl)alkan-1-ones 1 with DDQ
R
Yield of product [%]
2
3
4
5
1a
1b
1c
1d
1e
1f
Me
Et
i-Pr
t-Bu
Ph
40 – 60
38
41
ca. 30
49
50 – 60
5
6
3
7 – 9
1 – 2
–
–
–
1 – 2
6 – 9
ca. 16
22
ca. 1
1
2 – 3
–
CF3
–
Table 2. Oxidation of 1-(5-Alkyl-3,8-dimethylazulen-1-yl)ethanones 1a and 1h and of 5-Unsubstituted 1g
with DDQ
R’
Yield of product [%]
2
3
4
5
1a
1h
1g
i-Pr
Et
H
40 – 60
49
52
5
5
5
6
4
14
3
1
< 1
described oxidation protocol (Scheme 5). Indeed, this 1-(azulen-1-yl)ethanone stayed
almost untouched, and no product formation was observed. The same behavior was
observed for 1k with a t-Bu group at C(3)3).
3
)
Also no blue-product formation was observed with 1k.

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Helvetica Chimica Acta – Vol. 93 (2010)
Scheme 5
2.3. Mechanistic Considerations. There is little doubt that the bis(azulenylmethyl)-
substituted compounds 5 are the pivotal key in the events of the oxidation of 1-(3,8-
dimethylazulen-1-yl)alkan-1-ones with DDQ since on methanolysis they undergo,
without the appearance of any further intermediates, rearrangement to the pentacyclic
compounds type 3.
The oxidation of 1-methylazulenes and comparable azulenes with DDQ to the
corresponding azulenyl-1-methyl4) cations is a well established procedure (cf. [2] and
lit. cit. there), whereby, in a first step, an electron is transferred from the azulene to
DDQ (see Scheme 6), followed by deprotonation to yield the corresponding azulenyl-
1-methyl radical, which then is further oxidized to the azulenyl-1-methyl cation. The
present investigation teaches us that at least 1-acylazulene radical cations with Me
groups at C(3) and C(8) can lose a H-atom at MeꢀC(3) as well as MeꢀC(8) to form
the corresponding radicals (Scheme 6)4). The product yields realized by oxidation of
the 1-(3,8-dimethylazulen-1-yl)alkan-1-ones 1a, 1f, and 1g allow to estimate for these
cases a product ratio of ca. 10 :1 for the corresponding azulenyl-3-methyl4) and
azulenyl-8-methyl4) radicals. Since we observed no further oxidation products of the 8-
methyl group, we conclude that the azulenyl-8-methyl radicals as such are trapped by
DDQ or DDQ radical anions, resulting by single-electron transfer (SET) from the
azulenes to DDQ. It means that there are two imaginable reaction paths for the
.
formation of the key intermediates of type 5. Either the intermediate radical 1g(8) is
captured by DDQ or combines with the radical anion of DDQ. In the first case, the
.
.
formed addition radical 8g can then trap 1g(3) to yield 5g or the other way around
.
(not shown in Scheme 6), i.e., DDQ captures the radical 1g(3) , followed by
.
recombination with 1g(8) . In the second case, the first step yields the anion 8gꢀ,
which then leads to the formation of 5g by C-alkylation with 1g(3)þ. As a summary,
it can be said that the formation of the 3-(hydroxymethyl)azulene derivatives 7 in
the presence of DDQ and H2O does not require necessarily the occurrence of
azulenyl-3-methyl cations of type 1g(3)þ, generated by SET between the correspond-
ing radicals and DDQ. Azulene derivatives 7 can also be formed by hydrolysis of the
mono- or bis-adducts of 3-acylazulenyl-1-methyl4) radicals and DDQ according to
Scheme 6.
4
)
For convenience, the locant in the names azulenyl-1-methyl, azulenyl-3-methyl, and azulenyl-8-
methyl refers to the position of the Me group in the starting azulene derivative. The discussed
reaction paths in Schemes 6 and 7 are formulated with 1g, which bears the necessary substituents at
C(1), C(3), and C(8) for the observed product patterns (cf. Scheme 2).

Helvetica Chimica Acta – Vol. 93 (2010)
1553
Hydrolysis of the azulenyl-1-methyl substituent at C(1) of the 3,6-dioxocyclohex-4-
ene-1,2-dicarbonitriles 5 yields the 1,1-disubstituted 6-oxocyclohexa-2,4-dien-1,2-dicar-
bonitriles 8 with a CN group as strong p-acceptor substituent at C(2) (Scheme 7). It
seems that these intermediates are the starting point of the subsequent cascade
reactions, initiated by a most probably reversible intramolecular electrophilic addition
of C(6)¼O at C(3) of the azulen-4-ylmethyl substituent via a six-membered transition
state, leading to the zwitterionic intermediate 9g5). This intermediate carries at
neighbored C-atoms an acyl and an oxido group, so that the acyl group can easily
migrate under charge compensation and ester formation to the oxido group. Thus,
formed 10g is structurally perfectly disposed for a transannular C-acylation of the
former C(2) of 8g under formation of 11g. Intermediate 11g represents a 1,3-diketone,
which generally can undergo the so-called acid cleavage under base catalysis. The
catalyst in the present case can only be H2O, which forms reversibly with 11g the
hydrate 12g. The latter undergoes the acid cleavage, most probably by an intra-
molecular Hþ transfer from the hydrate to the neighbored acyl group, thus leading to
cleavage and formation of enol 13g. The new structure is again ideally arranged for an
intramolecular Michael addition – elimination reaction, whereby the pyran ring of 14g
is formed. The rigid structure of 14g induces finally a facile intramolecular ester
formation to 3g. The experiment with 5a and CD3OD (Scheme 4) shows that the
described cascade of reactions can also be induced and kept running in this solvent,
which indicates that also corresponding ketals of type 12g undergo the ring cleavage
reaction to intermediates of type 13g6)7).
The obtained yields of the pentacycles 5 are low and may depend on the production
rates of the azulenyl-4-methyl radicals in comparison to those of the azulenyl-1-methyl
radicals, which are responsible for the formation of the carboxaldehydes 2 and also for
the triketones 4. It seems that from a stererochemical viewpoint the intramolecular
electrophilic addition reaction to the zwitterionic intermediates of type 9g is the most
critical one since the alkyl residues of the acyl group determine the addition step. The
established row of increasing steric demands in the series Me, Et, i-Pr, and t-Bu is
grosso modo followed, since the pentacyclic compounds 3 are formed up to the i-Pr
5
)
There are principally two stereochemically different intramolecular addition modes, one, which is
sterically favored, leads to a trans arrangement of the neighbored Ac and oxido groups, a spatial
situation that would not allow an intramolecular migration of the Ac group, and the other one,
which places the Ac and oxido group in cis relation, ideally positioned for a migration of the Ac
group concomitantly with the formation of 9g, a driving force that may counterbalance the sterically
less favorable interactions in the transition state of bond-formation to 9g, which just slips in 10g.
The AM1-calculated DHf8 values of 8g and 10g show a difference of 10 kcal molꢀ1 in favor of the
latter.
6
7
)
It should be noted that HCl is formed in the course of the formation of the pyran ring. In other
words, the reaction cascade is most probably autocatalyzed by HCl.
)
It is of interest to note that all AM1-calculated structures of the reaction cascade 8g ! 14g exhibit
distances of the involved reactive centers of < 3.5 ꢃ, which seems to be a necessary spatial
requirement for a smoothly ongoing step-by-step reaction without interference with the
surrounding milieu. G. M. J. Schmidt and co-workers realized some time ago a similar empirical
rule for [2 þ 2] cycloaddition reactions of cinnamic acids and related compounds in solid-state
photochemistry, where the crystallographically controlled, critical intermolecular distance of the
reacting centers was found to have to be < 4.1 ꢃ, otherwise no cyclobutane-ring formation
occurred on irradiation of the crystals [3] (see also [4]).

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Helvetica Chimica Acta – Vol. 93 (2010)
Scheme 6
group (Tables 1 and 2). The pivaloyl residue of 1d still allows the formation of 5d, but
not any more that of the cascade product 3d. It is also of interest to note that with
increasing steric hindrance of the acyl groups, also the amount of triketones 4 is growing
(Tables 1 and 2).
To explain the formation of the triketones 4, we first thought that they might arise
.
from the dimerization of the azulenyl-1-methyl radicals 1(3) , followed by oxidative
decarbonylation (Scheme 8). Indeed, when separately synthesized 15a (see Exper.
Part) was subjected to the standard oxidative procedure with DDQ, triketone 4a,

Helvetica Chimica Acta – Vol. 93 (2010)
1555
Scheme 7
accompanied by major amounts of the tetraketone 16a, could be isolated in minor
amounts (cf. [5] for similar results). However, since the oxidation of 1a with DDQ
under the same conditions gave nearly three-times the amount of 4a but no tetraketone
16a at all, the postulated pathway for the formation of 4a could not be a main route to
4a in the course of the oxidation of 1a.
A second possibility for the formation of 4, which we envisaged, was the occurrence
of the corresponding 3-acylazulene-1-carboxylic acid as precursor, after we had found
trace amounts of 1,1’-(methylenediazulene-3,1-diyl)bis[ethanones] in the original
reaction mixtures. We prepared therefore the azulenecarboxylic acid 17a by oxidation
of 2a with KMnO4 (Scheme 9). Indeed, when we oxidized 1a with DDQ in acetone/
H2O in the presence of the acid, we obtained the triketone 4a in a yield of 26%,
accompanied by 55% of 2a, and 6% of the 1,1’-(methylenediazulene-3,1-diyl)bis-
[ethanone] 18a (Scheme 9). The latter could be converted quantitatively into 4a by
treatment with DDQ in acetone/H2O. This experiment convinced us that CH2-bridged
bis-azulenes of type 18 are key intermediates for the formation of the triketones 4,
following the pathways depicted in Scheme 10.

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Helvetica Chimica Acta – Vol. 93 (2010)
Scheme 8
Later on, we learned that Scheme 10 reflects only one half of the mechanistic
reality8).
3. Concluding Remarks. – We think that beside the disclosure of an unusual cascade
reaction, it is of importance to realize that soft azulen-1-ylmethyl cations may serve as
mobile protecting groups, e.g., to trap reactive enols in their keto form, which can easily
be removed again in protic solvents such as H2O or MeOH by formation of azulene-1-
methanols or their methyl ethers.
We are thankful to Rolf Schindler, Christoph Oberli, and Petra Wolint for experimental assistance, to
our NMR laboratory for specific NMR measurements, our MS laboratory for mass spectra, and our
laboratory for microanalysis for elemental analyses. Great thanks go also to Anthony Linden, who solved
for us the X-ray crystal structure of compound 3a. Financial support of this work by the Swiss National
Science Foundation is gratefully acknowledged.
8
)
See the subsequent communication on the synthesis of nonsymmetrically substituted bis(azulen-1-
yl) ketones [6].

Helvetica Chimica Acta – Vol. 93 (2010)
1557
Scheme 9
Scheme 10
Experimental Part
General. All solvents were distilled before use, or when necessary dried over Na/benzophenone and
then distilled, with the exception of solvents of p.a. quality from Merck, toluene, acetone, and AcOH.
Dioxane was filtered through Alox (act. I; ICN) prior to distillation. [13C2]AcCl (99%; Cambridge

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Helvetica Chimica Acta – Vol. 93 (2010)
Isotope Lab.) was diluted with AcCl to 25 mol-% 13C. M.p.: FP-52 and FP-5 with microscope (Mettler);
not corrected. TLC: Polygramꢅ sheets (Macherey-Nagel) covered with silica gel (SiO2) N-HR/UV2549) or
alumina N/UV254. Column chromatography (CC): basic Alox (act. III, ICN; method A) and SiO2 60 (40 –
63 and 60 – 200 mm; Merck; method B). Low-pressure LC (method C): SiO2 columns (Merck; Lichroprep
Si 60) equipped with a He tank (5 bar max.) and a differential refractometer R 401 (Waters Associates).
UV/VIS Spectra: Lambda-19 instrument (Perkin-Elmer); lmax and lmin in nm, log e in parentheses. IR
Spectra: Perkin-Elmer spectrophotometers FT-IR 1600 and Spectrum One; ˜n in cmꢀ1. NMR Spectra:
Bruker instruments AC-300, ARX-300, and AMX-600; assignments of the signals by 1H,13C correlations
(HSQC and HMBC), and in addition by COSY, NOESY, and INADEQUATE measurements; d
(CHCl3) 7.26, d (CHCl3) 77.0, d (C6HD5) 7.16, and d (C6D6) 128.0. MS (70 eV): MAT-SSQ-700 (Finnigan)
instrument (EI) and MAT 112S (Varian) instrument (CI); in m/z (rel. %).
1. 1-(3,8-Dimethylazulen-1-yl)alkan-1-ones. 1.1. Acylation of Guaiazulene. To a stirred soln. of
guaiazulene and the corresponding anhydride was added dropwise the Lewis acid (see Table 3). After the
reaction, hydrolysis was performed by addition of EtOH and H2O. The products were then extracted with
several portions of t-butyl methyl ether (t-BuOMe). The combined t-BuOMe extracts were washed with
H2O or aq. NaHCO3 soln. and with sat. NaCl soln. and then dried (Na2SO4). The residue was purified by
CC (method B) and then subjected to bulb-to-bulb distillation under high vacuum.
1.2. Acetylation of Guaiazulene Analogs. Half of the used amount of Et2O was cooled to ꢀ 608 or
ꢀ 708. At this temp., SnCl4 and Ac2O were added dropwise. To the resulting milky suspension, the
corresponding azulene dissolved in the second half of Et2O, was added dropwise. The workup procedure
was the same as described under 1.1. The results are summarized in Table 4.
2. Oxidation of the 1-(Azulen-1-yl)alkan-1-ones with DDQ in Aqueous Acetone: General Procedure.
As reported in [1], however, in ten times higher concentration and mostly with 5 – 10 mmol of the
azulenes. The products 2 – 5 were isolated and purified by chromatographic methods as described under
General; for average yields of pure material, see Tables 1 and 2.
2.1. 1-(5-Isopropyl-3,8-dimethylazulen-1-yl)ethanone (1a). Products 2a, 3a, 4a, and 5a. 3-Acetyl-7-
isopropyl-4-methylazulene-1-carboxaldehyde (2a): Dark red crystals. M.p. 84 – 858 (hexane). Rf (toluene/
t-BuOMe 4 :1) 0.38. IR (CHCl3): 3008m, 2967m, 1649vs, 1509s, 1447s, 1421s, 1391s, 1373s, 960w, 880m.
1H-NMR (600 MHz, C6D6): 10.25 (d, 4J(6,8) ¼ 2.2, HꢀC(8)); 10.24 (s, CHO); 7.85 (s, HꢀC(2)); 7.09 (dd,
4
3
3J(5,6) ¼ 10.9, J(6,8) ¼ 2.2, HꢀC(6)); 6.95 (d, J(5,6) ¼ 10.9, HꢀC(5)); 2.78 (s, MeꢀC(4)); 2.73 (sept.,
.
J ¼ 6.9, Me2CHꢀC(7)); 2.38 (s, MeCOꢀC(3)); 1.09 (d, J ¼ 6.8, Me2CHꢀC(7)). EI-MS: 254 (29, Mþ ),
239 (100, [M ꢀ Me]þ), 224 (8), 211 (8), 165 (18), 152 (21).
(6aRS,13bSR)-3-Chloro-10-isopropyl-5,12-dimethyl-2-oxo-2H-cyclohept[1,7]indeno[4,5-c]furo[3,2-
b]pyran-6,6a(7H)-dicarbonitrile (3a ¼ X(1)): Blue prisms (toluene/hexane). M.p. ca. 2158 (dec.). Rf
(toluene/t-BuOMe 4 :1) 0.76. UV/VIS (hexane): max. 588 (2.75), 374 (3.82), 355 (3.75), 363 (sh, 3.69),
306 (sh, 4.32), 299 (4.47), 294 (4.47), 246 (4.54), 208 (4.32); min. ca. 419 (2.11), 363 (3.67), 320 (3.40), 274
(4.20), 223 (4.23). IR (CHCl3): 2964m, 2222w (C ꢁ N), 1792vs (C¼O), 1691s, 1631m, 1452m, 1428w,
1387m, 1322s, 1302w, 1169w, 1129w, 998s, 971s. 1H-NMR (300 MHz, CDCl3): 8.29 (d, 4J(9,11) ¼ 1.5,
HꢀC(11)); 7.69 (dd, 3J(8,9) ¼ 11.3, 4J(9,11) ¼ 1.3, HꢀC(9)); 7.44 (s, HꢀC(13)); 7.24 (d, 3J ¼ 10.4,
HꢀC(8)); 4.11, 3.91 (AB, 2J(A,B) ¼ 16.6, CH2(7)); 3.17 (sept., J ¼ 6.9, Me2CHꢀC(10)); 2.62 (s,
MeꢀC(12)); 2.10 (s, MeꢀC(5)); 1.41 (d, J ¼ 6.9, Me2CHꢀC(10)). 13C-NMR (150 MHz, CDCl3): 164.54
(C(5)); 163.72 (C(2)¼O); 161.45 (C(3a)); 144.93 (C(10)); 137.37 (C(9)); 137.29 (C(11a)); 135.89
(C(7a)); 135.77 (C(11)); 133.78 (C(11b)); 133.20 (C(13)); 126.55 (C(12)); 125.78 (C(8)); 115.40 (N ꢁ
CꢀC(6a)); 113.13 (N ꢁ CꢀC(6)); 109.24 (C(13a)); 102.57 (C(3)); 89.64 (C(6)); 74.33 (C(13b)); 40.19
(C(6a)); 38.90 (Me2CHꢀC(10)); 37.02 (C(7)); 24.69, 24.67 (Me2CHꢀC(10)); 19.22 (MeꢀC(5)); 12.53
(MeꢀC(12)). CI-MS: 433.1 and 431.1 (33 and 100, [M þ H]þ). Anal. calc. for C25H19ClN2O3 (430.89): C
69.69, H 4.44, N 6.50, Cl 8.23; found C 69.79, H 4.51, N 6.12, Cl 9.04.
The structure of 3a was finally established by an X-ray crystal-structure analysis (Fig. 1 and Table 5)10).
9
)
)
Not specifically mentioned in the text.
10
CCDC-669699 contains the supplementary crystallographic data for 3a. These data can be obtained
free of charge from the Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/
data_request/cif.

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Helvetica Chimica Acta – Vol. 93 (2010)
Table 5. Crystallographic Data of 3a
Crystallized from
Empirical formula
Mr
Crystal color, habit
Crystal dimensions [mm]
Temperature [K]
Crystal system
Lattice type
Space group
Z
Reflections for cell determination
2q Range for cell determination [8] 38 – 40
toluene/hexane
C25H19ClN2O3
430.89
F(000)
1792
1.306
0.203
w/2q
55
5435
5026
0.030
3506
281
Dx [g cmꢀ3
]
m(MoKa) [mmꢀ1
Scan type
]
blue, prism
0.30 ꢂ 0.30 ꢂ 0.45 2q(max) [8]
173 (1)
monoclinic
C-centered
C2/c (#15)
8
Total reflections measured
Symmetry-independent reflections
Rint
Reflections used (I > 2s(I))
Parameters refined
Reflection/parameter ratio
Final R
25
12.5
0.0598
0.0547
Unit cell parameters
wR
a [ꢃ]
b [ꢃ]
c [ꢃ]
a [8]
b [8]
g [8]
V [ꢃ3]
23.784 (3)
Weights: p in w ¼ [s2(Fo) þ (pFo)2]ꢀ1 0.005
10.222 (2)
18.751 (3)
90
106.073 (9)
90
Goodness of fit
2.503
Secondary extinction coefficient
Final Dmax/s
D1 (max; min) [e ꢃꢀ3
1.9(2) · 10ꢀ7
0.0001
]
0.65; ꢀ 0.67a)
0.003 – 0.006
Range of s(d(CꢀC)) [ꢃ]
4381 (1)
a) Near-disordered i-Pr group.
1,1’-[Carbonylbis(5-isopropyl-8-methylazulene-3,1-diyl)]bis[ethanone] (4a ¼ X(2)): Red crystals.
M.p. 186 – 1878 (EtOH). Rf (toluene/t-BuOMe 4 :1) 0.28. UV/VIS (hexane): max. 524 (3.31), 407
(4.40), 395 (sh, 4.39), 308 (4.73), 250 (4.69); min. 455 (3.15), 355 (4.11), 270 (4.27). IR (CCl4): 2964m,
2930w, 2871w, 1663s, 1597m, 1505s, 1442s, 1405s, 1368m, 1302w, 1219w, 1191s, 1158w, 956w, 887m.
1H-NMR (300 MHz, CDCl3): 9.75 (d, 4J(4,6) ¼ 2.1, HꢀC(4)); 8.33 (s, HꢀC(2)); 7.81 (dd, 3J(6,7) ¼ 10.9,
4J(4,6) ¼ 2.1, HꢀC(6)); 7.66 (d, 3J(6,7) ¼ 10.9, HꢀC(7)); 3.23 (sept., J ¼ 6.9, Me2CHꢀC(5)); 2.96 (s,
MeꢀC(8)); 2.69 (s, MeCOꢀC(1)); 1.39 (d, J ¼ 6.9, Me2CHꢀC(5)). 13C-NMR (75 MHz, CDCl3): 196.97
(MeCOꢀC(1)); 189.06 (C¼O); 151.50 – 126.49 (20 azulene C)11); 38.35 (Me2CHꢀC(5)); 30.35
.
(MeCOꢀC(1)); 29.10 (MeꢀC(8)); 24.35 (Me2CHꢀC(5)). EI-MS: 478 (100, Mþ ), 463 (74, [M ꢀ
Me]þ), 435 (57, [M ꢀ MeCO]þ), 393 (19), 253 (12), 239 (24), 224 (15), 211 (12), 165 (13). Anal. calc.
for C33H34O3 (478.63): C 82.81, H 7.16; found: C 82.96, H 7.10.
(1RS,2RS)-1-[(3-Acetyl-7-isopropyl-4-methylazulen-1-yl)methyl]-2-[(3-acetyl-7-isopropyl-1-meth-
ylazulen-4-yl)methyl]-4,5-dichloro-3,6-dioxocyclohex-4-ene-1,2-dicarbonitrile (5a ¼ X(3)): Dark red
crystals (EtOH). M.p. ca. 2508 (dec.). Rf (toluene/t-BuOMe 4 :1) 0.48. IR (CHCl3): 2966m, 1707s,
1648m, and 1625m (C¼O), 1397vs, 1371s. 1H-NMR (500 MHz, CD2Cl2): 8.13 (d, 4J(6’’,8’’) ¼ 2.1,
HꢀC(8’’)); 7.76 (s, HꢀC(2’’)); 7.72 (d, 4J(6’,8’) ¼ 2.0, HꢀC(8’)); 7.55 (dd, 3J(5’’,6’’) ¼ 10.7, 4J(6’’,8’’) ¼ 2.1,
3
HꢀC(6’’)); 7.44 (br. d, not resolved, 3J(5’,6’) ¼ 10.8, HꢀC(6’)); 7.44 (d, J(5’’,6’’) ¼ 10.8, HꢀC(5’’)); 7.42
3
2
(s, HꢀC(2’)); 7.23 (d, J(5’,6’) ¼ 10.9, HꢀC(5’)); 5.10, 4.34 (AB, J(A,B) ¼ 13.9, CH2ꢀC(2)); 4.08, 3.79
(AB, 2J(A,B) ¼ 15.1, CH2ꢀC(1)); 3.00 (sept., J ¼ 6.9, Me2CHꢀC(7’’)); 2.87 (sept., J ¼ 6.9,
Me2CHꢀC(7’)); 2.56 (s, MeꢀC(4’)); 2.35 (s, MeꢀC(1’’)); 2.32 (s, MeCOꢀC(3’)); 2.32 (s,
MeCOꢀC(3’’)); 1.22, 1.21 (2d, J ¼ 6.9, Me2CHꢀC(7’’)); 1.16, 1.15 (2d, J ¼ 6.9, Me2CHꢀC(7’)).
2
2
1H-NMR (300 MHz, C6D6): 5.71, 4.66 (AB, J(A,B) ¼ 13.8, CH2ꢀC(2)); 4.00, 3.78 (AB, J(A,B) ¼ 15.1,
CH2ꢀC(1)). 13C-NMR (125 MHz, CD2Cl2): 196.30 (MeCOꢀC(3’)); 194.54 (MeCOꢀC(3’’)); 179.26
(C(6)¼O); 176.50 (C(3)¼O); 151.23 (C(4’)); 149.82 (C(7’’)); 147.24 (C(7’)); 145.24 (C(8a’’)); 144.92
Here and in the following part, only the 13C-signals at lowest and highest field of the azulene core
are given.
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Helvetica Chimica Acta – Vol. 93 (2010)
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(C(2’’)); 143.95 (C(5)); 142.97 (C(4)); 142.12 (C(2’)); 140.99 (C(8a’)); 140.23 (C(3a’’)); 138.26 (C(6’));
137.59 (C(3a’)); 137.31 (C(6’’)); 137.16 (C(4’’)); 136.36 (C(8’’)); 134.68 (C(8’)); 134.10 (C(5’’)); 133.75
(C(5’)); 128.52 (C(3’)); 127.00 (C(1’’)); 125.70 (C(3’’)); 115.24 (N ꢁ CꢀC(1)); 114.96 (N ꢁ CꢀC(2));
114.96 (C(1’)); 61.02 (C(2)); 59.56 (C(1)); 46.69 (CH2ꢀC(2)); 38.54 (Me2CHꢀC(7’)); 38.53
(Me2CHꢀC(7’’)); 37.38 (CH2ꢀC(1)); 30.76 (MeCOꢀC(3’’)); 30.35 (MeCOꢀC(3’)); 28.84 (MeꢀC(4’));
24.52, 24.40 (Me2CHꢀC(7’’)); 24.29, 23.85 (Me2CHꢀC(7’)); 13.00 (MeꢀC(1’’)). CI-MS
(C42H38Cl2N2NaOþ4 /C42H40Cl2N2NaO4þ ): 727.4 (69), 725.4 (36), 729.4 (100), 730.4 (45), 731.3 (52),
732.4 (21), 733.3 (14), 734.4 (6); calc. rel. % for a ca. 1:1 ratio of [M þ Na]þ and [MH2 þ Na]þ:
57:27:100 :46 :53 :22 :11:3. Anal. calc. for C42H38Cl2N2O4 (705.68): C 71.49, H 5.43, N 3.97; found: C
71.66, H 5.72, N 3.88.
2.1.1. Solvolysis of 5a. When 5a (0.02 g) was dissolved in MeOH or [2H3]MeOD (0.4 ml each) at r.t.,
the color of the soln. changed rapidly from red to blue (5a ! 3a). Workup by chromatography gave pure
3a and as a second, slower-moving component, the methyl or [2H3]methyl ether derivative 6 of 1-[3-
(hydroxymethyl)-5-isopropyl-8-methylazulen-1-yl]ethanone. No D had been incorporated in 3a in the
experiment with [2H3]MeOD.
1-[5-Isopropyl-3-(methoxymethyl)-8-methylazulen-1-yl]ethanone (6, R ¼ H; Scheme 4): Violet oil. Rf
(hexane/t-BuOMe 2 :1) 0.30. 1H-NMR (300 MHz, C6D6): 8.60 (d, 4J(4,6) ¼ 2.1, HꢀC(4)); 7.85 (s,
HꢀC(2)); 7.12 (dd, partly superimp. by the signal of C6HD5, 3J(6,7) ꢃ 11, 4J(4,6) ¼ 2.1, HꢀC(6)); 6.94 (d,
3J(6,7) ¼ 10.9, HꢀC(7)); 4.75 (s, CH2ꢀC(3)); 3.18 (s, MeO); 2.98 (s, MeꢀC(8)); 2.74 (sept., J ¼ 6.9,
.
Me2CHꢀC(5)); 2.52 (s, MeCOꢀC(1)); 1.13 (d, J ¼ 6.9, Me2CHꢀC(5)). EI-MS: 270 (41, Mþ ), 255 (34,
[M ꢀ Me]þ), 239 (100, [M ꢀ MeO]þ).
1-[5-Isopropyl-3-([2H3]methoxymethyl)-8-methylazulen-1-yl]ethanone (6, R ¼ D; Scheme 4).
.
1H-NMR (300 MHz, C6D6): As above, but no signal at 3.18 (MeO). EI-MS: 273 (45, Mþ ), 258 (34,
[M ꢀ Me]þ), 239 (100, [M ꢀ [2H3]MeO]þ).
2.1.2. 1-(5-Isopropyl-3,8-dimethylazulen-1-yl)[13C2]ethanone (1a*)12). Products 2a*, 3a*, and 5a*. 3-
[13C2]Acetyl-7-isopropyl-4-methylazulene-1-carboxaldehyde (2a*): 1H-NMR (300 MHz, CDCl3): 2.77
(dd, 1J(1H,13C) ¼ 127.4, 2J(1H,13C) ¼ 5.8, MeCOꢀC(3)). 13C-NMR (75 MHz, CDCl3): 196.68 (d,
1J(13C,13C) ¼ 42.8, MeCOꢀC(3)); 30.19 (d, 1J(13C,13C) ¼ 42.8, MeCOꢀC(3)).
(6aRS,13bSR)-3-Chloro-10-isopropyl-5-[13C]methyl-12-methyl-2-oxo-[5-13C]-2H-cyclohept[1,7]in-
deno[4,5-c]furo[3,2-b]pyran-6,6a(7H)-dicarbonitrile (3a*): 1H-NMR (300 MHz, CDCl3): 2.12 (2.10)
(dd, 1J(1H,13C) ¼ 130.3, 2J(1H,13C) ¼ 7.3, MeꢀC(5)). 13C-NMR (75 MHz, CDCl3): 19.23 (19.18) (d,
1J(13C,13C) ¼ 51.8, MeꢀC(5)); 164.60 (164.59) (d, 1J(13C,13C) ¼ 51.8, C(5)).
(1RS,2RS)-1-[(3-[13C2]Acetyl-7-isopropyl-4-methylazulen-1-yl)methyl]-2-[3-[13C2]acetyl-7-isoprop-
yl-1-methylazulen-4-yl)methyl]-4,5-dichloro-3,6-dioxocyclohex-4-ene-1,2-dicarbonitrile (5a*). Identified
by Rf on TLC. Not further analyzed.
2.2. 1-(5-Isopropyl-3,8-dimethyl-1-yl)propan-1-one (1b). Products 2b, 3b, 4b, and 5b. 7-Isopropyl-4-
methyl-3-(1-oxopropyl)azulene-1-carboxaldehyde (2b)13): Red crystals. M.p. 56 – 578 (pentane). Rf
(CH2Cl2/AcOEt 100 :1) 0.20. IR (CHCl3): 1648vs. 1H-NMR (300 MHz, CDCl3): 3.12 (q, J ¼ 7.4,
MeCH2COꢀC(3)); 1.31 (t, J ¼ 7.4, MeCH2COꢀC(3)). 13C-NMR (75 MHz, CDCl3): 35.99
.
(MeCH2COꢀC(3)); 9.37 (MeCH2COꢀC(3)). EI-MS: 268 (21, Mþ ), 239 (100). Anal. calc. for
C18H20O2 (268.35): C 80.57, H 7.51; found: C 80.53, H 7.62.
(6aRS,13bSR)-3-Chloro-5-ethyl-10-isopropyl-12-methyl-2-oxo-2H-cyclohept[1,7]indeno[4,5-c]furo-
[3,2-b]pyran-6,6a(7H)-dicarbonitrile (3b): Blue crystals. M.p. ca. 2608 (dec.). Rf (CH2Cl2/AcOEt 100 :1)
0.54. IR (CHCl3): 2222w, 1794vs, 1693s. 1H-NMR (300 MHz, CDCl3): 2.42, 2.30 (2 dq, 2J ꢃ 15.0, 3J ¼ 7.5,
MeCH2ꢀC(5)); 0.91 (t, 3J ¼ 7.5, MeCH2ꢀC(5)). 13C-NMR (75 MHz, CDCl3): 26.43 (MeCH2ꢀC(5));
10.66 (MeCH2ꢀC(5)). CI-MS (NH3): 447 and 445 (34 and 100, [M þ H]þ). Anal. calc. for C26H21ClN2O3
(444.92): C 70.19, H 4.76, N 6.30; found: C 70.54, H 4.93, N 5.89.
12
)
)
1H-NMR (300 MHz, CDCl3): 2.74 (2.72) (dd, 1J(H,13C) ¼ 130.7, 2J(H,13C) ¼ 6.2, MeCOꢀC(1)).
13C-NMR (75 MHz, CDCl3): Table 3.
For the following compounds of the 1b – 1f series, normally only the most important changes of the
spectroscopic data due to the change of the acyl group are given.
13

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Helvetica Chimica Acta – Vol. 93 (2010)
1,1’-[Carbonylbis(5-isopropyl-8-methylazulene-3,1-diyl)]bis[propan-1-one] (4b): Red crystals. M.p.
136 – 1398 (EtOH). Rf (CH2Cl2/AcOEt 100 :1) 0.07. IR (CHCl3): 1652s, 1589m. 1H-NMR (300 MHz,
CDCl3): 3.02 (q, J ¼ 7.4, MeCH2COꢀC(1)); 1.27 (t, J ¼ 7.4, MeCH2COꢀC(1)). 13C-NMR (75 MHz,
CDCl3): 197.07 (EtCOꢀC(1)); 189.11 (C¼O); 36.12 (MeCH2COꢀC(1)); 9.58 (MeCH2COꢀC(1)). EI-
.
MS: 506 (43, Mþ ), 477 (82, [M ꢀ Et]þ), 239 (100, [M ꢀ C18H19O2]þ). Anal. calc. for C35H38O3 (506.67): C
82.97, H 7.56; found: C 81.84, H 7.58.
(1RS,2RS)-1-{[7-Isopropyl-4-methyl-3-(1-oxopropyl)azulen-1-yl]methyl}-2-{[7-isopropyl-1-methyl-
3-(1-oxopropyl)azulen-4-yl]methyl}-4,5-dichloro-3,6-dioxocyclohex-4-ene-1,2-dicarbonitrile (5b): Red
crystals. M.p. ca. 2508 (dec.). IR (CHCl3): 1708s, 1647m, and 1624m (C¼O). 1H-NMR (300 MHz,
C6D6): 2.74 (br. q, J ꢃ 7.0, MeCH2COꢀC(3’,3’’)); 1.25 (t, 3J ¼ 7.2, MeCH2COꢀC(3’)); 1.20, 1.15 (2 d, J ¼
6.9, Me2CHꢀC(7’’)); 1.12 (t, 3J ¼ 7.3, MeCH2COꢀC(3’’)); 0.99 (d, J ¼ 6.9, Me2CHꢀC(7’)). 13C-NMR
(75 MHz, C6D6): 35.89 (MeCH2COꢀC(3’)); 35.28 (MeCH2COꢀC(3’’)); 9.10 (MeCH2COꢀC(3’,3’’)).
ESI-MS (NaI): 759, 757, 755 ([M þ Na]þ). Anal. calc. for C44H42Cl2N2O4 (733.73): C 72.03, H 5.77, N 3.82;
found: C 71.74, H 6.07, N 3.56.
2.3. 1-(5-Isopropyl-3,8-dimethylazulen-1-yl)-2-methylpropan-1-one (1c). Products 2c, 3c, 4c, and 5c.
7-Isopropyl-4-methyl-3-(2-methyl-1-oxopropyl)azulene-1-carboxaldehyde (2c): Red crystals. M.p. 69 –
1
728. Rf (CH2Cl2/AcOEt 100 :1) 0.16. IR (CHCl3): 1645vs. H-NMR (300 MHz, CDCl3): 3.59 (sept., J ¼
6.9, Me2CHCOꢀC(3)); 1.31 (d, J ¼ 6.9, Me2CHCOꢀC(3)). 13C-NMR (75 MHz, C6D6): 39.83
.
(Me2CHCOꢀC(3)); 19.52 (Me2CHCOꢀC(3)). EI-MS: 282 (8, Mþ ), 239 (100, [M ꢀ i-Pr]þ). Anal.
calc. for C19H22O2 (282.38): C 80.82, H 7.85; found: C 80.52, H 7.97.
(6aRS,13bSR)-3-Chloro-5,10-diisopropyl-12-methyl-2-oxo-2H-cyclohept[1,7]indeno[4,5-c]furo[3,2-
b]pyran-6,6a(7H)-dicarbonitrile (3c): Blue crystals (hexane). M.p. ca. 2508 (dec.). IR (CHCl3): 2221w,
1795s, 1693s. 1H-NMR (300 MHz, CDCl3): 2.80 (sept., J ¼ 6.8, Me2CHꢀC(5)); 1.19, 0.61 (2d, J ¼ 6.8,
Me2CHꢀC(5)). 13C-NMR (300 MHz, CDCl3): 32.47 (Me2CHꢀC(5)); 18.90, 18.73 (Me2CHꢀC(5)). EI-
.
MS: 460 and 458 (35 and 100, Mþ ). Anal. calc. for C27H23ClN2O3 (458.94): C 70.66, H 5.05, N 6.10; found:
C 70.84, H 5.16, N 6.00.
1,1’-[Carbonylbis(5-isopropyl-8-methylazulene-3,1-diyl)]bis[2-methylpropan-1-one] (4c): Red crys-
tals. M.p. 190.0 – 190.58 (heptane). Rf (toluene/t-BuOMe 4 :1) 0.59. IR (CHCl3): 1657s, 1588m. 1H-NMR
(300 MHz, CDCl3): 3.46 (sept., J ¼ 6.9, Me2CHCOꢀC(1)); 1.26 (d, J ¼ 6.9, Me2CHCOꢀC(1)). 13C-NMR
(75 MHz, CDCl3): 39.88 (Me2CHCOꢀC(1)); 19.47 (Me2CHCOꢀC(1)). CI-MS (NH3): 535 (100, [M þ
H]þ). Anal. calc. for C37H42O3 (534.73): C 83.11, H 7.92; found: C 82.70, H 8.01.
(1RS,2RS)-1-{[7-Isopropyl-4-methyl-3-(2-methyl-1-oxopropyl)azulen-1-yl]methyl}-2-{[7-isoprop-
yl)-1-methyl-3-(2-methyl-1-oxopropyl)azulen-4-yl]methyl}-4,5-dichloro-3,6-dioxocyclohex-4-ene-1,2-di-
carbonitrile (5c): Red crystals. M.p. ca. 1608 (dec.). IR (CHCl3): 1709m, 1641m, and 1622m (C¼O).
1H-NMR (300 MHz, C6D6): 3.30 (br. m, 2 Me2CHCOꢀC(3’,3’’)); 2.77, 2.58 (sept., Me2CHꢀC(7’,7’’));
1.34 (d, J ¼ 6.8, 3 H, Me2CH); 1.27 – 1.13 (m, 15 H, Me2CH); 1.02, 1.01 (2d, J ¼ 6.8, 6 H, Me2CH).
13C-NMR (75 MHz, C6D6): 39.92, 39.24 (4 Me2CH); 20.62, 20.55, 19.90, 19.13 (4 Me2CH). ESI-MS (NaI):
787, 785, 783 ([M þ Na]þ). Anal. calc. for C46H46Cl2N2O4 (761.77): C 72.53, H 6.09, N 3.68; found: C 71.28,
H 6.13, N 3.59.
2.4. 1-(5-Isopropyl-3,8-dimethylazulen-1-yl)-2,2-dimethylpropan-1-one (1d). Products 2d, 4d, and 5d.
3-(2,2-Dimethyl-1-oxopropyl)-7-isopropyl-4-methylazulene-1-carboxaldehyde (2d): Red crystals. M.p.
1
100 – 1018. Rf (toluene/t-BuOMe 6 :1) 0.48. IR (CHCl3): 1647vs. H-NMR (300 MHz, CDCl3): 1.42 (s,
Me3CCOꢀC(3)). 13C-NMR (75 MHz, C6D6): 45.09 (Me3CCOꢀC(3)); 28.62 (Me3CCOꢀC(3)). EI-MS:
.
296 (5, Mþ ), 239 (100, [M ꢀ t-Bu]þ). Anal. calc. for C20H24O2 (296.40): C 81.04, H 8.16; found: C 81.05, H
8.16.
1,1’-[Carbonylbis(5-isopropyl-8-methylazulene-3,1-diyl)]bis[2,2-dimethylpropan-1-one] (4d): Red
1
crystals. M.p. 223 – 2248 (EtOH). Rf (toluene/t-BuOMe 6 :1) 0.56. IR (CHCl3): 1664s, 1584m. H-NMR
(300 MHz, CDCl3): 1.41 (d, J ¼ 6.9, Me2CHꢀC(5)); 1.39 (s, Me3CCOꢀC(1)). 13C-NMR (75 MHz,
CDCl3): 45.17 (Me3CCOꢀC(1)); 28.80 (Me3CCOꢀC(1)); 28.72 (MeꢀC(8)); 24.42 (Me2CHꢀC(5)). EI-
.
MS: 562 (8, Mþ ), 505 (100, [M ꢀ t-Bu]þ), 239 (99). Anal. calc. for C39H46O3 (562.78): C 83.23, H 8.24;
found: C 83.18, H 8.25.
(1RS,2RS)-1-{[3-(2,2-Dimethyl-1-oxopropyl)-7-isopropyl-4-methylazulen-1-yl]methyl}-2-{[3-(2,2-
dimethyl-1-oxopropyl)-7-isopropyl-1-methylazulen-4-yl]methyl}-4,5-dichloro-3,6-dioxocyclohex-4-ene-

Helvetica Chimica Acta – Vol. 93 (2010)
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1,2-dicarbonitrile (5d): 1H-NMR (300 MHz, C6D6): 2.80, 2.56 (2 sept., Me2CHꢀC(7’,7’’)); 1.38, 1.34 (2 s,
Me3CCOꢀC(3’,3’’)); 1.25, 1.20 (2 d, J ¼ 6.9, Me2CHꢀC(7’’)); 1.02 (t-like, J ꢃ 6.9, Me2CHꢀC(7’)).
2.5. (5-Isopropyl-3,8-dimethylazulen-1-yl)phenylmethanone (1e). Products 2e and 4e. 3-Benzoyl-7-
isopropyl-4-methylazulene-1-carboxaldehyde (2e): Red crystals. M.p. 99 – 1018 (hexane/AcOEt 10 :1). Rf
1
3
(hexane/AcOEt 2 :1) 0.37. IR (CHCl3): 1647vs. H-NMR (300 MHz, CDCl3): 7.96 (dd with f.s., J ꢃ 8.0,
4J ꢃ 1.3, Ho of Ph); 7.62 (tt, J ꢃ 7.4, J ꢃ 1.3, Hp of Ph); 7.51 (t with f.s., J ꢃ 7.9, Hm of Ph). 13C-NMR
(75 MHz, CDCl3): 132.30 (Cp of Ph); 130.50 (Cm of Ph); 128.45 (Co of Ph). CI-MS (NH3): 317 (100, [M þ
H]þ). Anal. calc. for C22H20O2 (316.39): C 83.51, H 6.37; found: C 83.66, H 6.33.
3
4
3
Bis(3-benzoyl-7-isopropyl-4-methylazulen-1-yl)methanone (4e): Red crystals. M.p. 220 – 2218
(EtOH). Rf (hexane/AcOEt 3 :1) 0.30. IR (CHCl3): 2966m, 2931w, 2872w, 1638m, 1597m, 1579m,
1506s, 1448s, 1409s, 1386m, 1372m, 1303w, 1164m, 1132w, 1062w, 1047w, 1025w, 1002w, 959m, 941w, 898w,
845s, 828w. 1H-NMR (300 MHz, CDCl3): 9.85 (d, 4J(6,8) ¼ 2.1, HꢀC(8)); 8.03 (s, HꢀC(2)); 7.88 (dd with
3
4
3
f.s., Jo ꢃ 8.0, Jm ꢃ 1.3, Ho of Ph); 7.80 (dd, J(5,6) ¼ 10.8, J(6,8) ¼ 2.1, HꢀC(6)); 7.58 (d, J(5,6) ¼ 10.9,
HꢀC(5)); 7.51 (tt, Jo ꢃ 7.4, Jm ꢃ 1.3, Hp of Ph); 7.35 (t with f.s., Jo ꢃ 7.9, Hm of Ph); 3.26 (sept., J ¼ 6.9,
Me2CHꢀC(7)); 2.82 (s, MeꢀC(4)); 1.42 (d, J ¼ 6.9, Me2CHꢀC(7)). 13C-NMR (75 MHz, CDCl3): 194.29
(PhCOꢀC(3)); 189.12 (C¼O); 150.44 – 126.44 (20 azulene C, 8 benzene C), 38.45 (Me2CHꢀC(7));
28.70 (MeꢀC(4)); 24.43 (Me2CHꢀC(7)). CI-MS (NH3): 603 (100, [M þ H]þ). Anal. calc. for C43H38O3
(602.77): C 85.68, H 6.35; found: C 85.45, H 6.53.
2.6. 2,2,2-Trifluoro-1-(5-isopropyl-3,8-dimethylazulen-1-yl)ethanone (1f). Product 2f. 7-Isopropyl-4-
methyl-3-(2,2,2-trifluoroacetyl)azulene-1-carboxaldehyde (2f). Red crystals. M.p. 73 – 748 (hexane). Rf
(toluene/t-BuOMe 4 :1) 0.60. IR (CHCl3): 1685m, 1659s. 1H-NMR (300 MHz, CDCl3): 10.27 (s, CHO);
4
5
3
4
10.05 (d, J(6,8) ¼ 2.1, HꢀC(8)); 8.63 (q, J(2,F) ¼ 2.0, HꢀC(2)); 7.98 (dd, J(5,6) ¼ 10.9, J(6,8) ¼ 2.2,
HꢀC(6)); 7.89 (d, 3J(5,6) ¼ 10.9, HꢀC(5)); 3.31 (sept., Me2CHꢀC(7)); 2.94 (s, MeꢀC(4)); 1.45 (d,
Me2CHꢀC(7)). 13C-NMR (75 MHz, CDCl3): 187.16 (CHO); 176.44 (q, 2J(F,C¼O) ¼ 33.9. CF3CO);
156.15 – 119.95 (10 azulene C with C(2) at 147.74 (q, 4J(F,C(2)) ¼ 3.4)); 117.30 (q, 1J(C,F) ¼ 289, CF3CO);
.
38.53 (Me2CHꢀC(7)); 29.18 (MeꢀC(4)); 24.36 (Me2CHꢀC(7)). EI-MS: 308 (29, Mþ ), 239 (100, [M ꢀ
CF3]þ). Anal. calc. for C17H15F3O2 (308.30): C 66.23, H 4.90; found: C 66.17, H 4.97.
2.7. 1-(3,8-Dimethylazulen-1-yl)ethanone (1g). Products 2g, 3g, 4g, and 5g. 3-Acetyl-4-methylazulene-
1-carboxaldehyde (2g): Red crystals. M.p. 149 – 1508 (EtOH). Rf (toluene/t-BuOMe 4 :1) 0.53. IR
(CHCl3): 1652vs. 1H-NMR (300 MHz, CDCl3): 10.31 (s, CHO); 9.84 (dd, 3J(7,8) ¼ 9.7, 4J(6,8) ¼ 1.2,
3
HꢀC(8)); 8.49 (s, HꢀC(2)); 7.92 (t with f.s., 3J(5,6) ꢃ J(6,7) ¼ 9.6, HꢀC(6)); 7.77 (d, 3J(5,6) ¼ 10.1,
3
HꢀC(5)); 7.73 (t, 3J(6,7) ꢃ J(7,8) ¼ 9.6, HꢀC(7)); 2.96 (s, MeꢀC(4)); 2.79 (s, MeCOꢀC(3)). 13C-NMR
(75 MHz, CDCl3): 197.40 (CHO); 186.66 (MeCOꢀC(3)); 154.18 – 124.09 (10 azulene C); 30.50
.
(MeCOꢀC(3)); 29.37 (MeꢀC(4)). EI-MS: 212 (24, Mþ ), 198 (55, [M ꢀ CH2]þ), 197 (100, [M ꢀ
Me]þ). Anal. calc. for C14H12O2 (212.25): C 79.22, H 5.70; found: C 79.24, H 5.96.
(6aRS,13bSR)-3-Chloro-5,12-dimethyl-2-oxo-2H-cyclohept[1,7]indeno[4,5-c]furo[3,2-b]pyran-
6,6a(7H)-dicarbonitrile (3g): Blue crystals (toluene/hexane). M.p. > 1008 (dec.). Rf (toluene/t-BuOMe
1
4 :1) 0.73. IR (CHCl3): 2223w (C ꢁ N), 1796vs (C¼O), 1691s, 1632m, 1361s, 987s. H-NMR (600 MHz,
3
CDCl3): 8.35 (d, 3J(10,11) ¼ 9.2, HꢀC(11)); 7.74 (t, 3J(10,11) ꢃ J(9,10) ¼ 10.0, HꢀC(10)); 7.48 (s,
3
3
3
HꢀC(13)); 7.35 (t, J(9,10) ꢃ J(8,9) ¼ 9.8, HꢀC(9)); 7.27 (d, J(8.9) ¼ 10.1, HꢀC(8)); 4.13, 3.93 (AB,
2J(A,B) ¼ 16.8, CH2(7)); 2.62 (s, MeꢀC(12)); 2.09 (s, MeꢀC(5)). 13C-NMR (75 MHz, CDCl3): 164.68
(C(5)); 163.70 (C(2)¼O); 161.45 (C(3a)); 138.67 – 124.24 (9 C); 115.34 (N ꢁ CꢀC(6a)); 113.06 (N ꢁ
CꢀC(6)); 110.77 (C(13a)); 102.72 (C(3)); 89.61 (C(6)); 74.18 (C(13b)); 40.20 (C(6a)); 37.24 (C(7));
.
19.19 (MeꢀC(5)); 12.54 (MeꢀC(12)). EI-MS: 390 and 388 (34 and 100, Mþ ), 257 (39). Anal. calc. for
C22H13ClN2O3 (388.81): C 67.96, H 3.37, Cl 9.12, N 7.20; found: C 68.04, H 3.40, Cl 9.08, N 7.08.
1,1’-[Carbonylbis(8-methylazulene-3,1-diyl)]bis[ethanone] (4g): Dark red crystals. M.p. 236 – 2388
(AcOEt). Rf (toluene/t-BuOMe 4 :1) 0.21. IR (CHCl3): 1660s, 1595m, 1563w. 1H-NMR (300 MHz,
3
CDCl3): 9.84 (dd, 3J(4,5) ¼ 9.9, 4J(4,6) ¼ 1.3, HꢀC(4)); 8.32 (s, HꢀC(2)); 7.92 (td, 3J(5,6) ꢃ J(6,7) ¼ 10.2,
3
HꢀC(6)); 7.69 (d, 3J(6,7) ¼ 10.4, HꢀC(7)); 7.61 (t, 3J(5,6) ꢃ J(4,5) ¼ 9.6, HꢀC(5)); 2.98 (s, MeꢀC(8));
2.71 (s, MeCOꢀC(1)). 13C-NMR (75 MHz, CDCl3): 197.78 (MeCOꢀC(1)); 189.01 (C¼O); 153.26 –
.
126.99 (20 azulene C); 30.70 (MeCOꢀC(1)); 29.41 (MeꢀC(8)). EI-MS: 394 (100, Mþ ), 379 (74,
[M ꢀ Me]þ), 351 (54, [M ꢀ MeCO]þ), 268 (31), 253 (66). Anal. calc. for C27H22O3 (394.47): C 82.21, H
5.62; found: C 81.23, H 5.45.

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Helvetica Chimica Acta – Vol. 93 (2010)
(1RS,2RS)-1-[(3-Acetyl-4-methylazulen-1-yl)methyl]-2-[(3-acetyl-1-methylazulen-4-yl)methyl]-4,5-
dichloro-3,6-dioxocyclohex-4-ene-1,2-dicarbonitrile (5g): Dark red powder. M.p. > 3008. Rf (toluene/t-
BuOMe 4 :1) 0.37. 1H-NMR (300 MHz, C6D6): 7.70 (d with f.s., 3J(7’’,8’’) ¼ 9.7, HꢀC(8’’)); 7.55 (d with f.s.,
3J(7’, 8’) ¼ 9.7, HꢀC(8’)); 7.52 (s, HꢀC(2’’)); 7.50 (s, HꢀC(2’)); 7.11 – 6.62 (HꢀC(5’,5’’), HꢀC(6’,6’’),
2
2
HꢀC(7’,7’’)); 5.66, 4.50 (AB, J(A,B) ¼ 13.7, CH2ꢀC(2)); 3.85, 3.65 (AB, J(A,B) ¼ 15.1, CH2ꢀC(1));
2.63 (s, MeꢀC(4’)); 2.34 (s, MeCOꢀC(3’)); 2.33 (s, MeCOꢀC(3’’)); 2.09 (s, MeꢀC(1’’)). 13C-NMR
(150 MHz, C6D6): 195.54 (MeCOꢀC(3’’)); 193.62 (MeCOꢀC(3’)); 179.38 (C(6)¼O); 176.09
(C(3)¼O); 46.81 (CH2ꢀC(2)); 36.65 (CH2ꢀC(1)); 30.72 (MeCOꢀC(3’’)); 30.23 (MeCOꢀC(3’));
29.16 (MeꢀC(4’)); 12.60 (MeꢀC(1’’)).
2.8. 1-(5-Ethyl-3,8-dimethylazulen-1-yl)ethanone (1h). Products 2h, 3h, 4h, and 5h. 3-Acetyl-7-ethyl-
4-methylazulene-1-carboxaldehyde (2h): Red crystals. M.p. 80.5 – 82.58 (EtOH). Rf (toluene/t-BuOMe
4 :1) 0.37. IR (CHCl3): 1649vs. 1H-NMR (300 MHz, CDCl3): 10.25 (s, CHO); 9.81 (d, 4J(6,8) ¼ 2.0,
HꢀC(8)); 8.58 (s, HꢀC(2)); 7.86 (dd, 3J(5,6) ¼ 10.8, 4J(6,8) ¼ 2.0, HꢀC(6)); 7.72 (d, 3J(5,6) ¼ 10.8,
HꢀC(5)); 2.97 (q, J ¼ 6.8, MeCH2ꢀC(7)); 2.88 (s, MeꢀC(4)); 2.74 (s, MeCOꢀC(3)); 1.40 (t, J ¼ 7.1,
MeCH2ꢀC(7)). 13C-NMR (75 MHz, CDCl3): 196.74 (CHO); 186.59 (MeCOꢀC(3)); 33.61
(MeCH2ꢀC(7)); 30.23 (MeCOꢀC(3)); 29.08 (MeꢀC(4)); 16.67 (MeCH2ꢀC(7)). EI-MS: 240 (29,
.
Mþ ), 225 (100, [MꢀMe]þ). Anal. calc. for C16H16O2 (240.30): C 79.97, H 6.71; found: C 79.65, H 6.64.
(6aRS,13bSR)-3-Chloro-10-ethyl-5,12-dimethyl-2-oxo-2H-cyclohept[1,7]indeno[4,5-c]furo[3,2-
b]pyran-6,6a(7H)-dicarbonitrile (3h): Blue crystals (toluene). M.p. 111.0 – 111.58. Rf (toluene/t-BuOMe
4 :1) 0.82. IR (CHCl3): 2222w (C ꢁ N), 1793vs (C¼O), 1710m, 1691s, 1631m. 1H-NMR (600 MHz,
CDCl3): 2.94 (q, J ¼ 7.0, MeCH2ꢀC(10)); 2.62 (s, MeꢀC(12)); 2.11 (s, MeꢀC(5)); 1.40 (t, J ¼ 7.0,
MeCH2ꢀC(10)). 13C-NMR (150 MHz, CDCl3): 164.59 (C(5)); 163.77 (C(2)¼O); 161.49 (C(3a)); 115.41
(N ꢁ CꢀC(6a)); 113.15 (N ꢁ CꢀC(6)); 109.30 (C(13a)); 102.60 (C(3)); 89.65 (C(6)); 74.32 (C(13b));
40.17 (C(6a)); 37.02 (C(7)); 34.37 (MeCH2ꢀC(10)); 19.18 (MeꢀC(5)); 17.18 (MeCH2ꢀC(10)); 12.51
(MeꢀC(12)). CI-MS (NH3): 419 and 417 (36 and 100, [M þ H]þ). Anal. calc. for C24H17ClN2O3 (416.86):
C 69.15, H 4.11, N 6.72; found: C 69.00, H 4.12, N 6.55.
1,1’-[Carbonylbis(5-ethyl-8-methylazulene-3,1-diyl)]bis[ethanone] (4h): Red crystals. M.p. 177 – 1788
(EtOH). Rf (toluene/t-BuOMe 4 :1) 0.27. IR (CHCl3): 1663s, 1596m, 1506s. 1H-NMR (300 MHz, CDCl3):
3.07 (q, J ¼ 7.5, MeCH2ꢀC(5)); 2.93 (s, MeꢀC(8)); 2.64 (s, MeCOꢀC(1)); 1.36 (t, J ¼ 7.5,
MeCH2ꢀC(5)). 13C-NMR (75 MHz, CDCl3): 196.97 (MeCOꢀC(1)); 189.11 (C¼O); 33.72
(MeCH2ꢀC(5)); 30.41 (MeCOꢀC(1)); 29.15 (MeꢀC(8)); 16.73 (MeCH2ꢀC(5)). EI-MS: 450 (66,
.
Mþ ), 435 (61, [M ꢀ Me]þ), 241 (100), 240 (74), 221 (34). Anal. calc. for C31H30O3 (450.58): C 82.64, H
6.71; found: C 81.38, H 6.56.
(1RS,2RS)-1-[(3-Acetyl-7-ethyl-4-methylazulen-1-yl)methyl]-2-[(3-acetyl-7-ethyl-1-methylazulen-4-
yl)methyl]-4,5-dichloro-3,6-dioxocyclohex-4-ene-1,2-dicarbonitrile (5h): Dark red crystals (AcOEt).
M.p. 165.5 – 166.08. Rf (toluene/t-BuOMe 4 :1) 0.55. IR (CHCl3): 1708s, 1649m, and 1626m (C¼O).
2
2
1H-NMR (300 MHz, C6D6): 5.62, 4.53 (AB, J(A,B) ¼ 13.8, CH2ꢀC(2)); 3.93, 3.78 (AB, J(A,B) ¼ 15.0,
CH2ꢀC(1)); 2.69 (s, MeꢀC(4’)); 2.49 (q with f.s., J ꢃ 7.5, MeCH2ꢀC(7’’)); 2.36 (q, partially covered by
the two signals of MeCO, J ꢃ 7.5, MeCH2ꢀC(7’)); 2.36 (2s, separated by < 0.01 ppm, MeCOꢀC(3’,3’’));
2.19 (s, MeꢀC(1’’)); 1.15 (t, J ꢃ 7.5, MeCH2ꢀC(7’’)); 0.98 (t, J ꢃ 7.5, MeCH2ꢀC(7’)). 13C-NMR (75 MHz,
C6D6): 195.33 (MeCOꢀC(3’’)); 193.53 (MeCOꢀC(3’)); 179.31 (C(6)¼O); 175.99 (C(3)¼O); 115.35
(N ꢁ CꢀC(1)); 114.87 (N ꢁ CꢀC(2)); 46.83 (CH2ꢀC(2)); 37.10 (CH2ꢀC(1)); 33.38 (MeCH2ꢀC(7’));
33.19 (MeCH2ꢀC(7’’)); 30.54 (MeCOꢀC(3’’)); 30.00 (MeCOꢀC(3’)); 28.87 (MeꢀC(4’)); 16.22
(MeCH2ꢀC(7’’)); 16.06 (MeCH2ꢀC(7’)); 12.69 (MeꢀC(1’’)). ESI-MS: 703, 701, and 699 ([M þ Na]þ),
475 ([(M ꢀ C16H17O) þ Na]þ). Anal. calc. for C40H34Cl2N2O4 (677.63): C 70.90, H 5.06, N 4.13; found: C
70.21, H 5.04, N 4.07.
3. Mechanistic Investigations on Triketone 4 Formation. 3.1. Oxidation of 1,1’-[Ethane-1,2-diylbis(5-
isopropyl-8-methylazulene-3,1-diyl)]bis[ethanone] (15a) with DDQ in Aqueous Acetone. 3.1.1. Synthesis
of 15a (cf. [11]). 3.1.1.1. 1-[3-(Dimethylamino)-5-isopropyl-8-methylazulen-1-yl)ethanone. A mixture of
AcOH (4 ml), paraformaldehyde (0.84 g, 2.80 mmol), and N,N,N’,N’-tetramethylmethanediamine
(0.28 ml, 3.77 mmol) was heated at 808 until a clear soln. was formed (ca. 20 min). This soln. was
added with a syringe to a soln. of 1-(5-isopropyl-8-methylazulen-1-yl)ethanone (1.022 g, 4.47 mmol;
m.p. 74.5 – 75.58; formed on decarbonylation of 2a with Wilkinsonꢄs catalyst in toluene at 1108 (cf. [6])) in

Helvetica Chimica Acta – Vol. 93 (2010)
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CH2Cl2 (23 ml) at 08. After stirring for 1 h at r.t., an additional small amount of N,N,N’,N’-
tetramethylmethanediamine (0.05 ml, 0.37 mmol) was added, and stirring was continued for 0.5 h until
no starting azulene was recognizable by TLC. Usual workup gave, after bulb-to-bulb distillation under
high vacuum, pure product (1.27 g, 99%). Violet crystals. M.p. 71 – 728.
3.1.1.2. Ammonium Iodide Formation. The ethanone from Exper. 3.1.1.1 (1.27 g) was dissolved in
EtOH (35 ml), and MeI (1.20 ml, 12.80 mmol) was added. The soln. was stirred for 2 h at r.t. EtOH was
distilled off and the residue dried in vacuo: corresponding ammonium iodide (1.90 g). Violet crystals.
M.p. > 808 (dec.).
3.1.1.3. Reduction of the Ammonium Iodide. The ammonium iodide from Exper. 3.1.1.2 (0.070 g,
0.16 mmol) was dissolved in DMF (10 ml), and Zn dust (0.354 g, 5.35 mmol; Fluka, purum) was
added14). The mixture was heated under stirring during 2 h at 808. After cooling, CH2Cl2 (50 ml) was
added, and the soln. was filtered and then washed three times with H2O (150 ml). After drying and
evaporation, the residue (0.082 g, green-blue oil) was separated by prep. TLC (SiO2): pure 15a (0.018 g,
46%). Blue crystals. M.p. 226 – 2288 (acetone). Rf (Alox, hexane/AcOEt 2 :1) 0.46. IR (CHCl3): 2965w,
1644s, 1578w, 1521m, 1491w, 1407s, 1373m, 932w, 861w, 804w. 1H-NMR (300 MHz, CDCl3): 8.15 (d,
4J(4,6) ¼ 2.1, HꢀC(4)); 7.89 (s, HꢀC(2)); 7.51 (dd, 3J(6,7) ¼ 11.0, 4J(4,6) ¼ 2.0, HꢀC(6)); 7.30 (d,
3J(6,7) ¼ 11.0, HꢀC(7)); 3.43 (s, CH2CH2); 2.94 (sept., J ¼ 6.9, Me2CHꢀC(5)); 2.87 (s, MeꢀC(8)); 2.66
(s, MeCOꢀC(1)); 1.25 (d, J ¼ 6.9, Me2CHꢀC(5)). 13C-NMR (75 MHz, CDCl3): 196.48 (MeCOꢀC(1));
149.00 – 127.51 (20 azulene C); 37.92 (Me2CHꢀC(5)); 30.42 (MeCOꢀC(1)); 29.14 (CH2CH2); 28.62
(MeꢀC(8)); 24.39 (Me2CHꢀC(5)). CI-MS (NH3): 479 (100, [M þ H]þ), 239 (8). Anal. calc. for
C34H38O2 (478.67): C 85.31, H 8.00; found: C 85.03, H 7.78.
Oxidation of 15a (cf. Scheme 8). Products 16a and 4a. 1,2-Bis(3-acetyl-7-isopropyl-4-methylazulen-1-
yl)ethane-1,2-dione (16a): Red crystals. M.p. 193 – 1958 (MeOH). Rf (Alox, hexane/AcOEt 2 :1) 0.36. IR
(KBr): 2962m, 2929w, 2870w, 1666s, 1613s, 1505s, 1441s, 1408s, 1393s, 1369s, 1305w, 1207m, 1181s, 1146w,
1061w, 1029w, 960m, 879m, 826w, 727s, 697m, 660w, 608w. 1H-NMR (300 MHz, CDCl3): 10.30 (d,
4J(6,8) ¼ 2.1, HꢀC(8)); 8.45 (s, HꢀC(2)); 7.91 (dd, 3J(5,6) ¼ 10.9, 4J(6,8) ¼ 2.1, HꢀC(6)); 7.77 (d,
3J(5,6) ¼ 10.9, HꢀC(5)); 3.34 (sept., J ¼ 6.9, Me2CHꢀC(7)); 2.91 (s, MeꢀC(4)); 2.66 (s, MeCOꢀC(3));
1.47 (d, J ¼ 6.9, Me2CHꢀC(7)). 13C-NMR (150 MHz, CDCl3): 197.04 (MeCOꢀC(3)); 191.04
(C(1,2)¼O); 153.85 – 118.71 (20 azulene C); 38.55 (Me2CHꢀC(7)); 30.29 (MeCOꢀC(3)); 29.16
(MeꢀC(4)); 24.51 (Me2CHꢀC(7)). ESI-MS (NaI): 529 (100, [M þ Na]þ). Anal. calc. for C34H34O4
(506.64): C 80.60, H 6.76; found: C 80.40, H 6.80.
3.2. Oxidation of 1a in the Presence of 3-Acetyl-7-isopropyl-4-methylazulene-1-carboxylic Acid
(17a). 3.2.1. Synthesis of 17a. To a soln. of carboxaldehyde 2a (0.177 g, 0.70 mmol) in acetone/H2O 9 :1
(13.5 ml) were added Na2CO3 (0.264 g, 2.49 mmol) and then gradually KMnO4 (0.283 g, 1.79 mmol). The
mixture was stirred for 1 h at r.t. The suspension was then treated with 10% aq. ascorbic acid. H2O and
acetone were distilled off. The residue was distributed between t-BuOMe (40 ml) and H2O (40 ml), and
ascorbic acid was added until two cleanly separated phases were formed. The aq. phase was two
additional times washed with t-BuOMe (20 ml each). The combined org. layers were washed with H2O
(5 ꢂ 30 ml) and then dried (Na2CO3). The residue of the t-BuOMe soln. was purified by CC (SiO2 (30 g),
toluene/EtOH 10 :1): 17a (0.143 g, 76%)15). Red-violet crystals. M.p. 184 – 1898 (pentane-2,4-dione). Rf
(hexane/t-BuOMe 1:1) 0.16. IR (CHCl3): 3528w, 2967m, 2933m, 2873w, 2728w, 2587w, 1652vs, 1528w,
1509s, 1456s, 1425m, 1409s, 1370s, 1254w, 1184m, 1143w, 1087w, 1071w, 1047w, 1015w, 966w, 953w, 911w,
1
4
900w, 871w, 827w. H-NMR (300 MHz, CDCl3): 12.0 (very br. s, OH); 9.95 (d, J(6,8) ¼ 2.0, HꢀC(8));
8.76 (s, HꢀC(2)); 7.81 (dd, 3J(5,6) ¼ 10.9, 4J(6,8) ¼ 2.0, HꢀC(6)); 7.65 (d, 3J(5,6) ¼ 10.9, HꢀC(5)); 3.27
(sept., J ¼ 6.9, Me2CHꢀC(7)); 2.93 (s, MeꢀC(4)); 2.78 (s, MeCOꢀC(3)); 1.43 (d, J ¼ 6.9,
Me2CHꢀC(7)). 13C-NMR (75 MHz, CDCl3): 196.98 (MeCOꢀC(3)); 170.46 (COOH); 151.58 – 113.40
(10 azulene C); 38.48 (Me2CHꢀC(7)); 30.18 (MeCOꢀC(3)); 29.16 (MeꢀC(4)); 24.48 (Me2CHꢀC(7)).
14
)
)
The yield of 15a dropped to 5% when the reduction of the iodide was performed with activated Zn
dust (pre-treated by washing with dil. HCl soln).
We applied the described procedure to the oxidation of a number of further azulene-1-
carboxaldehydes to the corresponding 1-carboxylic acids (cf. Table 6). The presence of Na2CO3 is
essential for the realization of acceptable yields of the acids.
15

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CI-MS (NH3): 271 (100, [M þ H]þ). Anal. calc. for C17H18O3 (270.33): C 75.53, H 6.71; found: C 75.52, H
6.72.
3.2.2. Oxidation of 1a in the Presence of 17a (cf. Scheme 9). Products 2a, 4a, and 18a. 1,1-
[Methylenebis(5-isopropyl-8-methylazulene-3,1-diyl)]bis[ethanone] (18a): Red crystals. Rf (hexane/
AcOEt 3 :1) 0.13. IR (CHCl3): 2965m, 2931w, 2871w, 1643s, 1521m, 1464w, 1408s, 1373m, 1303w, 959w,
1
4
918w, 867w, 819w. H-NMR (300 MHz, CDCl3): 8.42 (d, J(4,6) ¼ 2.1, HꢀC(4)); 7.83 (s, HꢀC(2)); 7.57
3
4
3
(dd, J(6,7) ¼ 11.0, J (4,6) ¼ 2.1, HꢀC(6)); 7.35 (d, J (6,7) ¼ 11.0, HꢀC(7)); 4.73 (s, CH2); 3.05 (sept.,
J ¼ 6.9, Me2CHꢀC(5)); 2.89, (s, MeꢀC(8)); 2.62 (s, MeCOꢀC(1)); 1.27 (d, J ¼ 6.9, Me2CHꢀC(5)).
13C-NMR (75 MHz, CDCl3): 196.63 (MeCOꢀC(1)); 149.28 – 126.86 (20 azulene C); 38.01
(Me2CHꢀC(5)); 30.40 (MeCOꢀC(1)); 28.64 (MeꢀC(8)); 26.14 (CH2); 24.47 (Me2CHꢀC(5)). EI-
.
MS: 464 (99, Mþ ), 449 (39, [M ꢀ Me]þ), 421 (100, [M ꢀ MeCO]þ), 372 (39), 325 (21), 217 (15). Anal.
calc. for C33H36O2 (464.65): C 85.30, H 7.81; found: C 85.21, H 7.80.
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Received January 25, 2010