Evidence for carbon-carbon meisenheimer-wheland complexes between superelectrophilic and supernucleophilic carbon reagents

Article abstract of DOI:10.1002/anie.200500238

(Chemical Equation Presented) Proposal accepted: NMR experiments have shown unequivocally that the previously only proposed zwitterionic carbon-carbon Meisenheimer-Wheland complexes are formed in the reaction of 4,6-dinitrobenzofuroxan (DNBF) with 1,3,5-tris(N,N-dialkylamino)benzenes. Increasing the temperature results in a rapid exchange between three homomeric forms of the complex (see scheme; NR₂ = piperidyl, morpholinyl, pyrrolidinyl).

Full text of DOI:10.1002/anie.200500238

Angewandte
Chemie
[
7]
plexes. This kind of adduct was, up until now, only proposed,
but not observed experimentally.
Addition of solutions of 1,3,5-tris(N-piperidyl)benzene
1), 1,3,5-tris(N-morpholinyl)benzene (2), or 1,3,5-tris(N-
(
pyrrolidinyl)benzene (3) in CD Cl to a solution of DNBF
2
2
in CD Cl at À708C in an NMR tube resulted in the signals of
2
2
1
the starting materials in the H NMR spectra disappearing
and the appearance of new signals, which are ascribed to
compounds 4, 5, and 6 (Scheme 1). Acidification of solutions
of 4 in [D ]DMSO by addition of DCl afforded a spectrum
6
containing exclusively the signals of the starting materials,
namely 1 (in a protonated form) and DNBF.
Reactive Intermediates
Evidence for Carbon–Carbon Meisenheimer–
Wheland Complexes between Superelectrophilic
and Supernucleophilic Carbon Reagents**
Carla Boga, Erminia Del Vecchio, Luciano Forlani,*
Andrea Mazzanti, and Paolo E. Todesco
Scheme 1. Reaction of 1,3,5-tris(N,N-dialkylamino)benzenes with
4,6-dinitrobenzofuroxan to produce carbon–carbon zwitterionic
complexes.
The observation, or the isolation (when it is possible), of
[
1a]
intermediates in nucleophilic aromatic substitution (S Ar;
N
the so-called Meisenheimer complexes M) and in electro-
[
1b,c]
philic aromatic substitution
(the so-called Wheland com-
Scheme 1 illustrates the observed reactions with forma-
plexes W) reactions is an important confirmation of the
proposed mechanisms. Our interest has, in the past, focused
tion of Wheland–Meisenheimer complexes 4–6, whose struc-
tures are in agreement with the spectral data obtained at low
temperature. Detailed analyses of the reaction products 4–6
by variable-temperature NMR spectroscopy revealed an
unexpected behavior of these W–M compounds which
deserves some special consideration. We describe herein the
study carried out on compound 6 in detail; similar behavior
was obtained with 4 and 5 (full spectral data for compounds 4–
6 are shown in Tables 1 and 2).
[
2]
on intermediates in the S Ar reaction and, more recently,
N
[
3]
also on electrophilic aromatic substitution reactions (Whe-
land intermediates). Both kinds of s complexes (M and W)
have appreciable stability when a number of strong electron-
withdrawing groups or electron-donating groups, respectively,
are present on the aromatic ring. 4,6-Dinitrobenzofuroxan
[
4]
(
1
DNBF) is a powerful carbon electrophilic reagent and
,3,5-tris(N,N-dialkylamino)benzenes are powerful carbon
The mixing of cooled (À708C) solutions of DNBF and
[
5]
nucleophilic reagents. Herein, we report that these couples
1,3,5-tris(N-pyrrolidinyl)benzene (3) in CD Cl afforded a
2
2
[
6,7]
1
act as superelectrophilic
and supernucleophilic reagents,
new product (6) immediately. The H NMR spectrum of this
solution (maintained at À708C) shows four separate signals in
the range d = 4.3–5.1 ppm, three of which correspond to the
three hydrogen atoms belonging to the tris(N-pyrrolidinyl)-
benzene moiety and one ascribed to the furoxanic ring. The
other hydrogen atom, which is hydrogen bonded to the
furoxanic ring, was found at d = 8.60 ppm (Table 1).
thus providing evidence of a carbon–carbon coupling reaction
with formation of Meisenheimer–Wheland zwitterionic com-
[*] Dr. C. Boga, Dr. E. Del Vecchio, Prof. Dr. L. Forlani, Dr. A. Mazzanti,
Prof. Dr. P. E. Todesco
Dipartimento di Chimica Organica “A. Mangini”
Facolta’ di Chimica Industriale
Universita’ di Bologna
Viale Risorgimento, 4-40136 Bologna (Italy)
Fax: (+39)051-209-3654
Direct proton to carbon correlation (gHSQC sequence,
Figure 1, left) obtained at À708C shows that two of the four
hydrogen atoms which resonate at d = 4.61 and 4.43 ppm are
connected to two carbon atoms at d = 87.22 and 88.28 ppm;
E-mail: forlani@ms.fci.unibo.it
2
these chemical shifts are in the range typical for sp -
[
**] This work was supported by the University of Bologna (ex 60%
MIUR and funds for selected research topics A.A. 2003–2004)
and the Ministero dell’Universitꢀ e della Ricerca Scientifica e
Tecnologica.
hybridized carbon atoms of 1,3,5-tris(N-pyrrolidinyl)benzene.
In contrast, the two remaining proton signals (d = 4.32 and
5.00 ppm) are connected directly to carbon atoms resonating
at d = 45.09 and 40.87 ppm, respectively, which is clear
Supporting information for this article is available on the WWW
under http://www.angewandte.org or from the author.
3
evidence for the sp hybridization of these carbon atoms.
Angew. Chem. Int. Ed. 2005, 44, 3285 –3289
DOI: 10.1002/anie.200500238
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1
Table 1: H NMR spectral data in CD Cl .
2
2
[
a]
[a]
Compound
T [8C]
+25
dH5
dH7
dH10
dH12
dH14
dNCH2
dothers CH2
1
6.00
3.00–3.10
1.60–1.70 (m, 12H),
1.46–1.56 (m, 6H)
3.75–3.82 (m, 12H)
(
m, 12H)
3.05–3.10
m, 12H)
3.19–3.27
m, 12H)
2
3
+25
+25
6.00
5.18
(
1.88–1.98 (m, 12H)
(
DNBF
4
+25
À70
9.11 (d, J=1.9 Hz)
8.77
8.84 (d, J=1.9 Hz)
4.97 (d, J=4.7 Hz)
4.68 (d, J=4.7 Hz)
5.26
5.22
5.11
5.22
2.70–4.25
m, 12H)
3.28–3.52
m, 12H)
1.30–1.95 (m, 18H)
1.60–1.80 (m, 18H)
(
[
b]
[b]
[b]
[b]
[b]
[b]
[b]
4
+ 25
8.78
5.15
5.22
(
5
5
6
À70
À25
À70
8.81
8.83
8.60
5.05 (d, J=3.8 Hz)
5.30
5.00 (d, J=3.6 Hz)
4.66
5.23
5.16
5.23
4.61
5.30
5.23
4.43
2.85–4.25 (m, 24H)
3.10–4.00 (m, 24H)
1.60–2.20 (m, 12H)
[
b]
4.32 (d, J=3.6 Hz)
2.70–4.25
m, 12H)
3.15–3.60
m, 12H)
(
[
b]
6
+25
8.67 (d, J=0.9 Hz)
5.14
4.58
4.58
4.58
1.80–2.15 (m, 12H)
(
[a] Interchangeable assignments. [b] Broad singlet.
[
9]
Proton to proton correlation obtained at À708C (gCOSY
sequence, Figure 1, right) shows that the signal at d =
.00 ppm is correlated with the furoxanic hydrogen atom at
d = 8.60 ppm and to one of the three tris(N-pyrrolidinyl)ben-
zene hydrogen atoms at d = 4.32 ppm (J = 3.6 Hz).
asymmetric carbon center (C7) and a “C center” (C10);
2
under these conditions the two CH atoms are diastereotopic
and thus appear as anisochronous signals in both the H and
C NMR spectra. The same effect can be observed for the
aromatic quaternary carbon atoms, which show three sepa-
rated signals, and for the pyrrolidinic rings (six signals for the
six a-nitrogen carbon atoms).
1
5
1
3
1
3
1
On raising the temperature, neither the C nor H NMR
spectra change until À308C (À308C and À408C for 4 and 5,
respectively). Above À308C the three signals ascribed to the
hydrogen atoms of the tris(N-pyrrolidinyl)benzene moiety
show line broadening as a result of an exchange process. The
signals coalesce at À18C and appear as a single signal at
+
208C (Figure 2). In contrast, the other signal (H7) always
remains sharp.
It is worth noting that the dynamic process observed is
reversible: warming the solution from À308C to room
temperature and cooling again to À308C gives a spectrum
that is identical to the starting one. Satisfactory line-shape
simulation (Figure 2) was obtained using only one rate
°
constant, which shows that DG is not constant with temper-
°
Figure 1. Left: gHSQC spectrum of compound 6 in CD Cl at À708C.
ature and indicates that the DS value is not negligible. An
2
2
[
10]
Right: gCOSY spectrum of compound 6 in CD Cl at À708C.
2
2
accurate analysis by means of the Eyring equation yields
° À1 °= °
DH = 22.7 Æ 0.2 kcalmol and DS 32 Æ 5 e.u. for 6 (DH =
À1
°=
°
1
0
7.6 Æ 0.2 kcalmol , DS 18 Æ 6 e.u. for 4 and DH = 10.4 Æ
À1 °=
.3 kcalmol , DS 10 Æ 6 e.u. for 5).
1
3
All the mentioned NMR data, recorded at À708C, agree
with a Wheland–Meisenheimer (W–M) structure that is
produced in the reaction between DNBF and tris(N-pyrroli-
The same dynamic process can also be observed in the C
NMR spectra: the coalescence of the three quaternary carbon
atoms C11, C13, and C15 can be clearly seen above À308C,
and they appear as a single line above À18C. However, the
coalescence and the single averaged line cannot be observed
for the three carbon atoms at d = 87.22, 88.28, and 45.09 ppm
because of the very large chemical shift difference between
the signals (a line width of about 3 KHz is expected assuming
DG ꢀ 13 kcalmol at room temperature). As in the proton
spectra, the fourth signal, belonging to the C7 atom of the
furoxanic ring, is always sharp irrespective of the temper-
[
8]
dinyl)benzene.
In the Wheland–Meisenheimer structure (Scheme 1) C12
2
3
and C14 are sp hybridized, while C10 and C7 are sp
1
3
hybridized, thus accounting for the two high-field C NMR
signals at d = 45.09 and 40.87 ppm, respectively. The presence
of two distinct hydrogen (and carbon) signals for the two
other CH groups (C12 and C14) of the tris(N-pyrrolidinyl)-
benzene can be easily explained because of the presence of an
°
À1
3
286
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Chemie
1
3
Table 2: C NMR spectral data in CD Cl .
2
2
[
a]
[a]
[a]
Comp.
T [8C]
dC4,C6,C8,C9
dC5
dC7
dC10
dC12,C14
dC11,C13,C15
dNCH2
dNCH2CH2
and NCH2CH2CH2
1
+25
99.32
99.32,
154.80
52.15
25.29,
26.94
99.32
2
+25
+25
+25
97.64
86.67
97.64,
7.64
154.06
150.67
50.72
48.46
67.69
26.12
9
3
86.67,
6.67
8
DNBF
116.65,
126.42
135.47
120.14
41.99
1
1
1
38.46,
45.19,
51.19
4
À70
109.61,
39.47
88.24,
90.09
158.51,
159.85,
159.89
48.33,
23.78,
24.22,
24.26,
24.56,
1
1
1
13.43,
19.28,
50.43
48.76 49.08,
49.80(2 sig. ov.),
49.85
2
2
2
2
2
4.88,
6.15,
6.26,
6.51,
7.33
4
5
+25
À70
110.92,
135.70
135.51
43.75
42.94
160.34
50.44
26.53,
24.72
1
1
1
14.21,
20.00,
51.21
109.44,
39.17
45.09
89.52,
91.23
159.87,
160.27,
160.94
46.75,
47.36,
47.60,
47.90,
65.00,
65.56,
66.12,
66.20,
66.56,
66.97
1
1
1
13.44,
18.34,
50.33
4
4
8.37,
8.71
6
6
À70
+25
109.36,
133.78
134.60
40.87
42.28
87.22,
88.28
154.91,
155.29,
157.94
47.54,
48.37,
48.86,
49.03,
24.83,
24.97,
25.01,
25.43,
25.88,
26.17
1
1
1
13.62,
19.16,
50.95
4
4
9.37,
9.55
[
b]
110.25,
157.86
49.79
25.96
114.54,
119.46,
151.79
[a] Interchangeable assignments. [b] Broad signals.
ature, thus showing that the furoxanic anion is still present at
room temperature.
possible explanation can be hypothesized by considering
the different steric environments involved in the W–M
complexes: although the steric effects of the six-membered
rings are almost the same in 4 and 5, the smaller and more
flexible five-membered rings in 6 lead to a stabilization
[
11]
Hence, the dynamic NMR data suggest the existence,
above the coalescence temperature, of a Wheland–Meisen-
heimer complex in three homomeric structures (Scheme 2)
with bonds C7/C10, C7/C12, and C7/C14 rapidly exchanging.
°
of the W–M structure and hence affords greater DH and
°
°
The positive value of DS also agrees with a mechanism in
DS values.
which a bond involved in the W–M complex is broken. It
should be noted that the activation parameters obtained
for 6 are quite different from those obtained for 4 and 5. A
The existence of a p–p charge-transfer (CT) complex
between DNBF and tris(amino)benzene derivatives could
also occur, but experimental spectral data obtained for
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zwitterionic carbon–carbon Meisenheimer–Wheland com-
plexes, whose structures were ascertained by one- and two-
dimensional NMR experiments. A dynamic NMR study of
these species also showed, through observation of coales-
cence, that increasing the temperature results in the forma-
tion of a Wheland–Meisenheimer complex in three homo-
meric structures with bonds C7/C10, C7/C12, and C7/C14
rapidly exchanging. Very strongly activated systems often give
unexpected results, and this is the case here.
Experimental Section
Compounds 1 and 2 were prepared as reported in ref. [3]. Compound
3
was prepared in a similar manner from 1,3,5-trichlorobenzene and
pyrrolidine. DNBF was prepared as reported in ref. [8]. NMR spectra
were recorded on Varian Gemini 300, Mercury 400, or Inova 600
1
spectrometers operating at 300, 400, or 600 MHz (for H NMR) or
1
3
7
5.46, 100.56, or 150.80 MHz (for C NMR), respectively. Signal
multiplicities were established by DEPTexperiments. Chemical shifts
were referenced to the solvent [(d = 5.30 and 54.2 ppm for CD Cl ),
2
2
(
d = 7.27 and 77.0 ppm for CDCl ), (d = 2.0 and 0.3 ppm for CD CN),
3
3
1
13
(d = 2.6 and 39.5 ppm for [D ]DMSO) for
H and C NMR,
6
respectively]. The variable-temperature NMR spectra and 2D low-
temperature spectra were recorded on the Inova 600 with a direct
PFG Probe. The temperatures were calibrated by substituting the
sample with a precision Cu/Ni thermocouple before the measure-
ments. Complete fitting of dynamic NMR line shapes was carried out
Figure 2. Left: experimental variable-temperature NMR spectra of 6.
Right: line-shape simulation obtained with the rate constant indicated.
[
12]
using a PC version of the DNMR-6 program.
NR =piperidyl, morpholinyl, pyrrolidinyl.
The low-temperature samples for NMR experiments were
prepared directly in the NMR tube by mixing two cooled (À708C)
solutions of DNBF (0.006m) and 1, 2, or 3 (0.006m) in CD Cl .
2
2
2
The behavior observed for compounds 4–6 on changing the
temperature and the reversibility of the process was also observed in
CDCl solutions.
3
Mixing 1, 2, or 3 with DNBF in acetonitrile at low temperature
(
À308C) resulted in the precipitation of a coral-red solid. Heating the
resulting solids, which were isolated by filtration, in a melting point
apparatus resulted in them gradually darkening (133–1408C, 118–
1
258C, and 129–1358C for compounds 4–6, respectively) then
1 13
decomposing. However, their H and C NMR spectra were identical
to those obtained for compounds 4–6, formed directly in an NMR
tube and recorded at 258C.
Received: January 21, 2005
Published online: April 18, 2005
Keywords: carbanions · carbocations · electrophilic addition ·
nucleophilic addition · zwitterions
Scheme 2. Proposed interconversion pathway for the observed reversi-
ble and temperature-dependent transformation of W–M structures
.
4–6.
[
1] a) M. B. Smith, J. March, Marchꢀs Advanced Organic Chemistry,
Reactions, Mechanisms, and Structure, 5th ed., Wiley, New York,
compounds 4 and 6 clearly show (also at room temperature)
2001, chap. 13, pp. 850 – 893, and references therein; b) M. B.
3
the presence of sp hybridization at the C7-position of the
Smith, J. March, Marchꢀs Advanced Organic Chemistry, Reac-
tions, Mechanisms, and Structure, 5th ed., Wiley, New York, 2001,
chap. 11, pp. 675 – 758, and references therein; c) D. Lenoir,
Angew. Chem. 2003, 115, 880 – 883; Angew. Chem. Int. Ed. 2003,
42, 854 – 857.
1
3
DNBF moiety ( C NMR signal at d = 40.87 ppm). If such a
CT complex existed, this carbon atom should revert back to
2
13
sp hybridization and hence a C NMR signal at around d =
9
+
1
3
0 ppm would be observed in the C NMR spectrum at
258C.
In conclusion, the reaction between a superelectrophilic
[
[
2] a) G. Collina, L. Forlani, J. Phys. Org. Chem. 1988, 1, 351 – 357;
b) L. Forlani, A. Ferrara, A. Lugli, P. E. Todesco, J. Chem. Soc.
Perkin Trans. 2 1994, 1703 – 1707; c) C. Boga, L. Forlani, J. Chem.
Soc. Perkin Trans. 2 1998, 2155 – 2157.
3] C. Boga, E. Del Vecchio, L. Forlani, Eur. J. Org. Chem. 2004,
1567 – 1571.
reagent such as DNBF and powerful carbon nucleophilic
reagents such as 1,3,5-tris(N,N-dialkylamino)benzenes have
given the possibility to characterize, for the first time,
3
288
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Chemie
[
4] F. Terrier, Nucleophilic Aromatic Displacement, VCH, New
York, 1991.
[
[
5] F. Effenberger, Acc. Chem. Res. 1989, 22, 27 – 35.
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Perkin Trans. 2 1995, 1629 – 1637; b) E. Buncel, R. A. Renfrow,
M. J. Strauss, J. Org. Chem. 1987, 52, 488 – 495.
[
7] a) S. Kurbatov, P. Rodrigues-Dafonte, R. Gaumont, F. Terrier,
Chem. Commun. 2003, 2150 – 2151; b) G. A. Olah, Angew.
Chem. 1993, 105, 805 – 827; Angew. Chem. Int. Ed. Engl. 1993,
32, 767 – 788.
[
8] Recently, we studied the formation of s complexes between
nitrobenzofuroxans and amines and found that reaction of
DNBF with 1,4-diazabicyclo[2.2.2]octane (DABCO) or piper-
1
idine affords Meisenheimer complexes which show H NMR
signals (in [D ]DMSO) corresponding to protons bonded to the
6
3
sp -hybridized C7 atom at d = 6.8 ppm and 6.2–6.4 ppm, respec-
tively. When DNBF reacts with 1,8-diazabicyclo[5,4,0]undec-7-
ene (DBU) the positive charge is delocalized over the two
1
3
nitrogen atoms, and the H NMR signal of the proton on the sp -
hybridized C7 atom appears at d = 5.3 ppm, which is very similar
to values reported here for 4–6; see C. Boga, L. Forlani, J. Chem.
Soc. Perkin Trans. 2 2001, 1408 – 1413.
[
9] a) W. B. Jennings, Chem. Rev. 1975, 75, 307 – 322; b) K. Mislow,
M. Raban, Top. Stereochem. 1967, 1, 1 – 38.
[
[
10] J. Sandstrꢁm, Dynamic NMR Spectroscopy, Academic Press,
London, 1982, p. 99.
11] This observation also excludes the hypothesis that the starting
reagents could be involved in the transition state because, if this
is true, an exchange between the H7 signal of the W–M complex
and the H7 signal of DNBF should be observed.
12] QCPE program no. 633, Indiana University, Bloomington, IN,
USA.
[
Angew. Chem. Int. Ed. 2005, 44, 3285 –3289
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