Nucleophilic reactivities of azulene and fulvenes

Article abstract of DOI:10.1002/ejoc.200801099

The kinetics of the reactions of azulene (1), 6,6-dimethylfulvene (2), 6-[4-(dimethylamino)phenyl]fulvene (3) and 6-(julolidin-9-yl)fulvene (4) with a set of benzhydrylium ions (reference electrophiles) have been investigated in MeCN. The second-order rat

Full text of DOI:10.1002/ejoc.200801099

FULL PAPER
DOI: 10.1002/ejoc.200801099
Nucleophilic Reactivities of Azulene and Fulvenes
Mariusz Kedziorek,[a] Peter Mayer,[a] and Herbert Mayr*[a]
˛
Dedicated to Professor Heinz Langhals on the occasion of his 60th birthday
Keywords: Carbocations / Aromaticity / Kinetics / Linear free energy relationships / UV/Vis spectroscopy / Nucleophilic
addition
The kinetics of the reactions of azulene (1), 6,6-dimethyl-
fulvene (2), 6-[4-(dimethylamino)phenyl]fulvene (3) and 6-
tionship logk2(20 °C) = s(N + E), the nucleophilicity param-
eters N and s of the π-nucleophiles 1–4 were determined and
(julolidin-9-yl)fulvene (4) with a set of benzhydrylium ions compared with those of other types of nucleophiles. Azulene
(reference electrophiles) have been investigated in MeCN.
The second-order rate constants for these reactions correlate
linearly with the electrophilicity parameters (E) of the benz-
(1, N = 6.66) is about 10 times more nucleophilic than N-
methylpyrrole and comparable to 2-methylindole.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
hydrylium ions. According to the linear free-enthalpy rela- Germany, 2009)
philes, we have studied the kinetics of their reactions with
Introduction
benzhydrylium ions (Ar2CH+), which we employ as refer-
ence electrophiles, following the previously established
methodology.[11] Because azulene incorporates the cross-
conjugated π-system of fulvenes, we have also studied the
nucleophilic properties of the 6-donor-substituted fulvenes
2–4.
Azulene is a 10-π-electron nonbenzenoid, nonalternant,
catacondensed, aromatic system with unique properties: a
deep blue color, a dipole moment of 1.08Ϯ0.02 D (in ben-
zene) and high reactivity towards electrophiles and nucleo-
philes.[1] As depicted in Scheme 1, these properties can be
explained by the polar resonance structures with a fused
tropylium cation and cyclopentadienyl anion. Being readily
available through Hafner’s elegant synthetic approach,[2]
azulene (1) and its derivatives became key compounds for
the study of nonbenzenoid aromaticity.[3–5]
We have previously reported that the reactions of carbo-
cations with π-systems follow the linear free-energy rela-
tionship [Equation (1)], where electrophiles are charac-
terized by one parameter [electrophilicity (E)], and nucleo-
philes are characterized by two parameters [nucleophilicity
(N) and slope (s)].[11–14]
log k2(20 °C) = s(N + E)
(1)
Scheme 1.
In this paper, we will show that the second-order rate
constants of the reactions of azulene (1) and the fulvenes
2–4 with benzhydrylium ions 5 (see Scheme 2 and Table 1)
can be described by Equation (1), which allows for the de-
termination of the N and s values of 1–4.
With pKBH+ = –1.66[6] and σ+arene = –1.60,[7] azulene can
be expected to be comparable to N-methylpyrrole (pKBH+
= –2.90,[8] σ+arene = –1.90[9]) and N-methylindole (pKBH+
=
–2.32,[10] σ+arene = –1.58[7]) in Brønsted basicity and reactiv-
ity towards electrophiles.
In order to include azulene in our comprehensive nucleo-
philicity scale, which allows for the direct comparison of
the reactivities of a large variety of π-, n- and σ-nucleo-
[a] Department Chemie und Biochemie, Ludwig-Maximilians-Uni-
versität München,
Butenandtstr. 5–13 (Haus F), 81377 München, Germany
Fax: +49-89-2180-77717
E-mail: herbert.mayr@cup.lmu.de
Supporting information for this article is available on the
WWW under http://www.eurjoc.org or from the author.
Scheme 2.
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Nucleophilic Reactivities of Azulene and Fulvenes
Table 1. Benzhydrylium ions Ar2CH+ (5) used as reference electro- column chromatography on neutral Al2O3 for its purifica-
philes in this study.
tion.
Ar2CH+ (5)[a]
R
E[b]
When fulvene 3 was combined with the less reactive
Entry
–
benzhydrylium salt (dma)2CH+BF4 (5b-BF4) in MeCN at
1
2
3
4
5
6
7
(pyr)2CH+ (5a)
(dma)2CH+ (5b)
(mpa)2CH+ (5c)
(mor)2CH+ (5d)
(dpa)2CH+ (5e)
(mfa)2CH+ (5f)
(pfa)2CH+ (5g)
–N(CH2)4
–NMe2
–NMePh
–N(CH2CH2)2O
–NPh2
–N(Me)CH2CF3
–N(Ph)CH2CF3
–7.69
–7.02
–5.89
–5.53
–4.72
–3.85
–3.14
r.t., the resulting NMR spectra indicated a fast consump-
tion of 3 with formation of a complex product mixture,
probably oligomers of 3. The cationic polymerization of
fulvenes induced by Brønsted acids has previously been re-
ported in the literature.[16–18]
The monosubstitution product 9 was obtained in 44%
yield by combining 2 equiv. of 3 and benzhydryl chloride
5h-Cl in CH2Cl2 at –80 °C (Scheme 5).
[a] Counterion: BF4 . [b] E values are from ref.[11]
–
Results
Product Characterization
The treatment of azulene (1, 4.3 equiv.) with 4,4Ј-bis(di-
methylamino)benzhydrylium tetrafluoroborate (5b-BF4) in
MeCN at r.t. yielded the monosubstitution product 6 in
59% and the bis-substitution product 7 in 41% yield
(Scheme 3).
Scheme 5.
Kinetic Investigations
The kinetic studies were conducted in MeCN at
20Ϯ0.1 °C under first-order conditions with a large excess
(Ͼ10 equiv.) of the nucleophiles 1–4 over the benz-
hydrylium ions 5. We followed the progress of the reactions
by UV/Vis spectroscopy with diode array spectrometers
equipped with fiber optics and a submersible probe; the
evaluation was performed at λmax of 5. We obtained the
first-order rate constants (kobs) from the exponential decays
of the UV/Vis absorbances of the electrophiles 5. Plots of
kobs versus the concentrations of the nucleophiles 1–4 were
linear with negligible intercepts (Figure 1), and their slopes
yielded the second-order rate constants (k2, Table 2). Slower
subsequent reactions of the initially formed adducts with
the excess of fulvenes caused an increase of the absorptions
Scheme 3.
Compounds 6 and 7 have previously been obtained from
1 and the corresponding benzhydryl alcohol 5b-OH in the
presence of acetic acid.[15]
Fulvene 3 and 4,4Ј-bis(morpholino)benzhydrylium tetra-
fluoroborate (5d-BF4) reacted in MeCN at –35 °C to give
12% of 8 (Scheme 4), the structure of which was confirmed
by single-crystal X-ray analysis.
Scheme 4.
Figure 1. Determination of the second-order rate constant for the
reaction of 5b (1.44ϫ10–5 ) with 4 in MeCN at 20 °C (k2
=
5.96 –1 s–1, the decay of the absorbance at 605 nm is shown for [4]
The low yield of 8 can be explained by its high sensitivity
towards acids. Because it decomposed on silica gel, we used = 8.89ϫ10–4 ).
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M. Kedziorek, P. Mayer, H. Mayr
˛
FULL PAPER
at the monitored wavelengths. Because these processes oc-
curred after the reactions under consideration, they did not
affect the kinetics reported in Table 2. We observed complex
kinetics in CH2Cl2 but did not evaluate further.
Table 2. Second-order rate constants (k2) for the reactions of the
electrophiles 5 with the nucleophiles 1–4 in MeCN at 20 °C and
resulting N and s parameters for 1–4.
Entry Nucleophile; N, s Electrophile[a]
k2 [–1 s–1]
1
2
3
4
5
6
7
8
1; 6.66, 1.02
(dma)2CH+ (5b)
(mor)2CH+ (5d)
(mfa)2CH+ (5f)
(mor)2CH+ (5d)
(dpa)2CH+ (5e)
(mfa)2CH+ (5f)
(pfa)2CH+ (5g)
(dma)2CH+ (5b)
(mpa)2CH+ (5c)
(mor)2CH+ (5d)
(mfa)2CH+ (5f)
(pyr)2CH+ (5a)
(dma)2CH+ (5b)
(mpa)2CH+ (5c)
(mor)2CH+ (5d)
4.29ϫ10–1
1.38ϫ101
7.36ϫ102
4.43ϫ10–2
2.37[b]
2; 3.93, 0.88
7.92ϫ10–1
6.66
3; 6.72, 0.87
4; 7.79, 1.06
4.88ϫ10–1
1.35ϫ101 [b]
1.38ϫ101
2.77ϫ102
1.34
9
10
11
12
13
14
15
5.96
1.93ϫ102 [b]
2.49ϫ102
–
[a] Counterion: BF4 . [b] Data not used for the calculation of N
and s values (see text).
Figure 2. Correlation of log k2 (20 °C, MeCN) for the reactions of
1–4 with the benzhydrylium ions 5 in relation to their electrophilic-
ity parameters E. – Points in parentheses were not used for the
correlations (see text).
Discussion
In order to determine the nucleophilicity parameters N
and s of the nucleophiles 1–4 according to Equation (1), we
plotted the logarithms of the second-order rate constants
(log k2) versus the E parameters of the corresponding elec-
trophiles. The plots for the reactions of azulene (1) and fulv-
enes 2–4 with the reference electrophiles 5 were linear,
though the benzhydrylium ions 5c and 5e showed system-
atic deviations (Figure 2).
Analogous deviations have previously been reported
when the reactions of these two carbocations with other
nucleophiles have been studied in MeCN.[19] Therefore, we
did not take into consideration the rate constants for 5c and
5e for calculations of the N and s parameters.
All correlation lines had slopes close to 1 as previously
reported for other π-nucleophiles (e.g. pyrroles,[19a] in-
doles[20] and alkenes[11]), which implies that the relative re-
activities of these compounds are almost independent of
the nature of the electrophiles. As a consequence, structure-
reactivity relationships can be based on the nucleophilicity
values, which are summarized in Figure 3.
According to Figure 3, azulene (1, N = 6.66) is consider-
ably more nucleophilic than 6,6-dimethylfulvene (2, N =
3.93) and is comparable to the [4-(dimethylamino)phenyl]-
substituted fulvene 3 (N = 6.72) and 2-methylindole (N =
6.91).[20] Azulene largely exceeds the nucleophilicity of 1,3-
dimethoxybenzene (N = 2.48) and 2-methylfuran (N =
3.61).[11]
Figure 3. Comparison of the nucleophilicities of azulene (1) and
fulvenes 2–4 (in MeCN) with those of other types of nucleophiles
(in CH2Cl2).
Figure 3 furthermore shows that 6,6-dimethylfulvene (2),
which yields a 1,1,2,5-tetraalkylpentadienyl cation by reac- of magnitude more nucleophilic than 2-methyl- or 4-methyl-
tion with an electrophile, is approximately 1 to 1.5 orders 1,3-pentadiene, which yield trialkylsubstituted allyl cations.
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Nucleophilic Reactivities of Azulene and Fulvenes
A comparison of 2 with cyclopentadiene (N = 2.30)[13] re-
veals that the extra isopropylidene group of 2 activates by
a factor of about 40.
pound 8. These data can be obtained free of charge from the Cam-
bridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/
data_request/cif.
Supporting Information (see also the footnote on the first page of
this article): Preparative procedures, product characterization, de-
tails of the individual runs of the kinetic experiments and crystal
data are available.
We obtained the N and s values for 1–4 given in Table 2
from their reactions with benzhydrylium ions. The question
arises whether these numbers are also useful for predicting
their reactivities toward other types of electrophiles. To the
best of our knowledge, so far only one system has been
reported that addresses this question. Terrier and co-
workers determined[21] a second-order rate constant of
5.88 –1 s–1 (MeCN, 25 °C) for the reaction of 4,6-dinitro-
benzofuroxane with azulene (1). From the electrophilicity
parameter of this electrophile (E = –5.06)[20] and the N and
s values of 1 given in Table 2, we calculated k2 as
42.9 –1 s–1 at 20 °C. Though the difference between calcu-
lated and experimental values will increase slightly when the
difference in reaction temperature is taken into account, it
is obvious that the deviation is considerably less than a fac-
tor of 102, which we consider satisfactory for a 3-parameter
correlation covering 40 orders of magnitude in reacti-
vity.[22,23]
Acknowledgments
Financial support by the Deutsche Forschungsgemeinschaft
(DFG) (SFB 749) and the Fonds der Chemischen Industrie is grate-
fully acknowledged. We thank Dr. A. R. Ofial for his assistance
during the preparation of the manuscript.
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Azulene (1) is the most nucleophilic neutral hydrocarbon
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arized structure (Scheme 1) has thus been quantified. The
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Experimental Section
General Section: Benzhydrylium tetrafluoroborates 5-BF4 (see
Table 1) were synthesized as described previously.[11] Benzhydryl
chloride 5h-Cl[26] and nucleophiles 1,[2] 2,[27] [28] and 4[28] were syn-
3
thesized according to literature procedures.
Kinetics: The kinetics of the reactions of the benzhydrylium ions
with the nucleophiles 1–4 were followed by UV/Vis spectroscopy
using a J&M TIDAS diode array spectrophotometer connected to
a Hellma 661.060-UV quartz Suprasil immersion probe (5 mm light
path) through fiber optic cables with standard SMA connectors.
All kinetic measurements were performed in Schlenk glassware un-
der nitrogen. The temperature of the solutions during the kinetic
studies was maintained at 20Ϯ0.1 °C with circulating bath cryo-
stats.
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X-ray Crystal Structure Analysis of 8: The data collection was per-
formed on a Nonius KappaCCD diffractometer equipped with a
rotating anode generator. The structure was solved by direct meth-
ods with SIR97[29] and refined with SHELXL-97.[30] CCDC-
706951 contains the supplementary crystallographic data for com-
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[25] For a database of reactivity parameters E, N, and s, see:
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Received: November 6, 2008
Published Online: January 16, 2009
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