Evidence of reversibility in azo-coupling reactions between 1,3,5-tris(N,N-dialkylamino)benzenes and arenediazonium salts

Article abstract of DOI:10.1021/jo071111k

(Chemical Equation Presented) The reactions between strongly electron-rich aromatic substrates (1,3,5-tris(N,N-dialkylamino)benzenes, neutral carbon super nucleophiles) and diazonium salts produce moderately stable σ complexes (Wheland complexes). The reactivity of Wheland complexes with electrophiles (other diazonium salts, or 4,7-dinitrobenzofuroxan) produces exchange reactions in the electrophilic part: the better electrophile replaces the less powerful electrophile. In the same way, in Wheland complexes with the 1,3,5-tris(morpholinyl)-benzene, the 1,3,5-tris(piperidinyl)benzene replaces the less powerful nucleophile 1,3,5-tris(morpholinyl)-benzene. Evidence is reported here indicating that for the title system the reaction of the attack of the electrophilic reagent producing Wheland complexes is a reversible process. The final products of the diazo-coupling reactions undergo a further attack of some diazonium salts. From the final products of the double diazo-coupling reactions (diazo compounds), we collected evidence that is a clear instance of complete reversibility of the diazo-coupling reaction.

Full text of DOI:10.1021/jo071111k

Evidence of Reversibility in Azo-Coupling Reactions between
1,3,5-Tris(N,N-dialkylamino)benzenes and Arenediazonium Salts
Carla Boga, Erminia Del Vecchio, Luciano Forlani,* and Silvia Tozzi
Dipartimento di Chimica Organica “A. Mangini”, ALMA MATER STUDIORUM-UniVersita` di Bologna,
Viale Risorgimento 4, 40136, Bologna, Italy
forlani@ms.fri.unibo.it
ReceiVed May 25, 2007
The reactions between strongly electron-rich aromatic substrates (1,3,5-tris(N,N-dialkylamino)benzenes,
neutral carbon super nucleophiles) and diazonium salts produce moderately stable σ complexes (Wheland
complexes). The reactivity of Wheland complexes with electrophiles (other diazonium salts, or 4,7-
dinitrobenzofuroxan) produces exchange reactions in the electrophilic part: the better electrophile replaces
the less powerful electrophile. In the same way, in Wheland complexes with the 1,3,5-tris(morpholinyl)-
benzene, the 1,3,5-tris(piperidinyl)benzene replaces the less powerful nucleophile 1,3,5-tris(morpholinyl)-
benzene. Evidence is reported here indicating that for the title system the reaction of the attack of the
electrophilic reagent producing Wheland complexes is a reversible process. The final products of the
diazo-coupling reactions undergo a further attack of some diazonium salts. From the final products of
the double diazo-coupling reactions (diazo compounds), we collected evidence that is a clear instance of
complete reversibility of the diazo-coupling reaction.
SCHEME 1. Generally Accepted Pathway of the SEAr
Introduction
The usually accepted pathway1,2 (reported also in textbooks3)
of the electrophilic aromatic substitution reaction is shown in
Scheme 1.
The first interaction between the electron-deficient reagent
and an electron-rich substrate affords a donor-acceptor com-
plex4,5 (or π complex, DA) by an equilibrium that is quickly
reached. The π complex evolves to the σ complex (Wheland
intermediate, W).6
Generally, the W formation is indicated to be the rate-
determining step of the overall reaction. The driving force of
the reaction is reported to be the re-aromatization process, which
is usually proposed as a fast and hardly reversible step.2,5
Our recent paper reports7 a clear instance of the slow proton
departure in a rate-determining step (from W to P), which
follows the fast attack of the electrophilic reagent to form the
W complex.
Even if the mechanism of this reaction has been extensively
investigated,1,8 in particular for the diazocoupling reaction9 there
are some aspects of this reaction which need further investiga-
tion, as some reported explanations are poorly supported by
experimental data and are not completely convincing. Evidence
of complete reversibility of the electrophilic aromatic substitu-
tion reaction concerns only a few cases as in sulfonation
reactions and in nitration reactions.10 An instance of the
reversible C-azo coupling reaction is described when the reaction
was carried out in the presence of p-toluenesulfonic acid.11
* Address correspondence to this author. Phone: +39 051 2093641. Fax:
+39 051 2093654.
(1) Taylor, R. Electrophilic Aromatic Substitution; John Wiley & Sons:
New York, 1990.
(2) (a) Hartshorn, S. S. R. Chem. Soc. ReV. 1974, 3, 167-193. (b) Hubig,
M.; Kochi, J. K. J. Am. Chem. Soc. 2000, 122, 8279-8288. (c) Hubig, S.
M.; Kochi, J. K. J. Org. Chem. 2000, 65, 6807-6818.
10.1021/jo071111k CCC: $37.00 © 2007 American Chemical Society
Published on Web 10/09/2007
J. Org. Chem. 2007, 72, 8741-8747
8741

Boga et al.
In a previous paper, we reported12 the characterization (mainly
by 1H NMR spectroscopy) of some moderately stable Wheland
intermediates obtained by the azo-coupling reaction between
1,3,5-tris(N,N-dialkylamino)benzenes and arenediazonium salts.
We now report some independent evidence on the reversibility
of the reaction between 1,3,5-tris(N,N-dialkylamino)benzenes
and different electrophilic reagents.
SCHEME 2
Results and Discussion
Previously, we described12 the reaction shown in Scheme 2
affording the W complexes 6 and 7. Final diazo compounds
8H and 9H are spontaneously obtained from W complexes. Free
bases 8 and 9 are obtained from W complexes by base catalysis
and, obviously, by treatment of salts 8H and 9H with bases.
The present investigation regards some different aspects of
the reaction steps reported in Scheme 1. In particular, the
reversibility of each step was investigated separately by different
experimental approaches which are reported in the following
subheadings.
1. Formation and Evolution of a Derivative Arising from
the Double Attack of a Diazonium Salt on 1. An interesting
1
behavior was observed in recording H NMR spectral data of
the 6b complex. When the reaction between 1,3,5-tris(N,N-
piperidinyl)benzene (1) and diazonium salt 4 (see Scheme 2) is
carried out directly in the NMR probe tube, in CD3CN at -30
°C with reagents in equimolar amount, without waiting for the
complete dissolution of 1, the only signals recorded by 1H NMR
spectroscopy are those related to compounds 10 (see Scheme
3) together with a very small amount (less than 5%) of the
related σ-complex 6b. Compound 6b arises from a double attack
of the electrophilic reagent on the substrate, which is in
temporary defect, together with signals related to starting
diazonium salt. Signals related to salt 10 slowly disappear as
solid 1 is dissolved. After about 10 min (in this time all of 1 is
dissolved) the only recorded signals where those related to W
complex 6b. Scheme 3 reports a reasonable explanation of the
observed behavior that involves the departure from 10 of the
diazonium salt 4.
SCHEME 3
(3) (a) Allinger, N. L.; Cava, M. P.; De Jongh, D. C.; Johnson, C. R.;
Lebel, N. A.; Stevens, C. L. Organic Chemistry; Worth Publishing: New
York, 1981. (b) Sykes, P. A Guidebook to Mechanism in Organic Chemistry;
Longman: London, UK, 1981. (c) Lowry, T. H.; Richardson, K. S.
Mechanism and Theory in Organic Chemistry; Harper and Row Publisher:
New York, 1987. (d) Taylor, R. Electrophilic Aromatic Substitution; John
Wiley & Sons: New York, 1990. (e) Carey, F. A.; Sundberg, R. J. AdVanced
Organic Chemistry Part A; Plenum Press: New York, 1990. (f) McMurry,
J. Organic Chemistry; Brooks/Cole: Phoenix, AR, 2004. (g) Brown, W.
H.; Foote, C. S.; Iverson, B. L. Organic Chemistry; Thomson Brooks/
Cole: Belmont, CA, 2005.
(4) Bockman, T. M.; Kosynkin, D.; Kochi, J. K. J. Org. Chem. 1997,
62, 5811-5820.
(5) Rosokha, S. V.; Kochi, J. K. J. Org. Chem. 2002, 67, 1727-1737.
(6) Lenoir, D. Angew. Chem., Int. Ed. 2003, 42, 854-857.
(7) Boga, C.; Del Vecchio, E.; Forlani, L.; Tocke Dite Ngobo, A.-L.;
Tozzi, S. J. Phys. Org. Chem. 2007, 20, 201-205.
2. Replacement of the Electrophilic Reagent Bonded to
Wheland Complexes. 2.a. Exchange of Diazonium Salt. The
investigation of the diazonium moiety exchange was carried out
directly in the NMR spectroscopy tube in CD3CN, at -30 °C.
After the time needed for the spectrum to show the disappear-
ance of the signals of the starting materials and the complete
formation of σ-complexes (6a-c or 7a-c, obtained from
mixtures of 1,3,5-tris(N,N-dialkylamino)benzenes 1 or 2 and
diazonium salts 3-5), the addition of another aryl diazonium
tetrafluoborate, different from that used to obtain σ-complexes,
may produce the exchange of the electrophilic reagent as
represented in Scheme 4. The results are summarized in Table
1.
(8) Smith, M. B.; March, J. March’s AdVanced Organic Chemistry,
Reactions, Mechanisms, and Structure, 5th ed.; Wiley: New York, 2001.
(9) (a) Zollinger, H. Acc. Chem. Res. 1973, 6, 335-341. (b) Zollinger,
H. In The Chemistry of Functional groups. The Chemistry of Amino, Nitroso,
Nitro and Related Groups. Suppl. F2s; Patai, S., Ed.; John Wiley & Sons:
New York, 1996; Part 2, Chapter 3.
The reactions reported in entries 1,2, 6-8, and 12 of Table
1 clearly indicate that the more powerful electrophile expels
the less powerful one. In the case of entries 3, 4, 9, and 10, the
replacement of the 4-nitrobenzendiazonium salt by the 4-bromo-
or 4-methoxybenzenediazonium tetrafluoroborate may be a
surprising behavior, but if the formation of the W complex is
a reversible process, the excess of the less able electrophilic
reagent may produce a partial replacement.
(10) Olah, G. A.; Narang, S. C.; Malhotra, R.; Olah, J. A. J. Am. Chem.
Soc. 1979, 101, 1805-1807.
(11) Mokrushin, S.; Bezmaternikh, M. A. MendeleeV Commun. 1998,
197-198.
(12) Boga, C.; Del Vecchio, E.; Forlani, L. Eur. J. Org. Chem. 2004,
1567-1571.
8742 J. Org. Chem., Vol. 72, No. 23, 2007

Reactions of Aromatic Substrates and Diazonium Salts
TABLE 1. Reactions of Wheland Complexes with Diazonium Salts
starting σ-complex
Y′ (added
diazonium salt)
obtained
σ-complex
Y (diazonium salt
leaving by exchange)
time,a
min
conv,
%
entry
(substituent)
1
2
6a (OCH3)
6a (OCH3)
6b (NO2)
6b (NO2)
6c (Br)
NO2
Br
OCH3
Br
OCH3
NO2
NO2
Br
OCH3
Br
6b
6c
6a
6c
6a
6b
7b
7c
OCH3
OCH3
NO2
NO2
Br
5
5
20
5
20
5
5
5
20
5
20
5
100
82
15
65
4
67
100
100
5
3b
4b
5c
6
6c (Br)
Br
7
8
7a (OCH3)
7a (OCH3)
7b (NO2)
7b (NO2)
7c (Br)
OCH3
OCH3
NO2
NO2
9c
10c
11c
12
7a
7c
10
0
82
OCH3
NO2
no reaction
7b
7c (Br)
Br
-
a The time of conversion is affected by the stability of σ-complexes. b Ratio of 6b:p-Y′ArN2+BF4- ) 1:2. c Ratio of starting σ-complex:p-Y′ArN2+BF4
) 1:5.
SCHEME 4
SCHEME 6
SCHEME 7
SCHEME 5
electrophilic reagent. In this case, the attack of the second
electrophilic reagent occurs in a different position with respect
to that occupied by the first electrophilic reagent with the
formation of a complex in which the two different electrophiles
are bonded to 1,3,5-tris(N,N-dialkylamino)benzene (di-W).
The second pathway is reported in Scheme 7. It concerns
the departure of the first arenediazonium salt to return to the
starting materials, followed by the addition of the second
diazonium salt on the 1,3,5-tris(dialkylamino)benzene, which
is in equilibrium with the Wheland complex. In this case the
addition of the second electrophile might occur on the same
position as the first one.
Since the three positions are equivalent in 1,3,5-tris(N,N-
dialkylamino)benzenes 1 or 2, it was not possible to discriminate
between the two pathways of Schemes 6 and 7. To have more
information, we synthesized the asymmetric compound 12 (4,4′-
(5-pyrrolidin-1-yl-1,3-phenylene)dimorpholine) with two non-
equivalent positions (Scheme 8).
A solution of diazonium salt 3 in CD3CN was then added to
a solution of 12 dissolved in CD3CN at -30 °C, directly in a
NMR spectroscopy tube. The main product of the reaction was
the σ complex 13a, as tested by 1H NMR spectral data (see the
Experimental Section) together with a small amount of the
complex bearing the arenediazonium moiety bonded in the ortho
position with respect to the pyrrolidinic ring (14a). After
complete formation of 13a, a solution in CD3CN of diazonium
salt 4 was added to the reaction mixture. The 1H NMR spectrum
immediately showed new signals ascribed to the complex 13b,
together with those related to the leaving arendiazonium salt 3
and, in a small percentage, with the complex bearing the
electrophile 4 in the ortho position with respect to the pyrro-
lidinic ring (14b). Obviously, the same complex 13b was also
obtained by direct reaction between 12 and 4.
2.b. Replacement of the Diazonium Moiety with a Super
Electrophilic Reagent: From a Wheland Complex to a
Wheland/Meisenheimer Complex (WM). When an equimolar
amount of 4,7-dinitrobenzofuroxan (DNBF) was added to a
solution (in CD3CN, directly prepared in the NMR tube, at -30
°C) of the Wheland complex 6a or 6b, the signals of the product
11, identical with those of the compound obtained by direct
mixing of solutions of DNBF and 1,13 appeared together with
the signals corresponding to the leaving arenediazonium (as
tetrafluoroborate salt, 4), as reported in Scheme 5.
The reactions represented in Scheme 5 are almost quantitative
and support the trend reported in the previous section 2.a, DNBF
being, also in this case, a better electrophilic reagent than the
diazonium salt 4.
2.c. Two Main Pathways To Explain Reactions Reported
in Schemes 4 and 5. To explain how the diazo moiety of
complexes 6a-c and 7a-c is replaced by another electrophilic
reagent, we can draw two main reaction pathways. The first
one is depicted in Scheme 6 and involves the dication formation
(di-W) which is followed by the departure of the first introduced
(13) Boga, C.; Del Vecchio, E.; Forlani, L.; Mazzanti, A.; Todesco, P.
E. Angew. Chem., Int. Ed. 2005, 44, 3285-3289.
J. Org. Chem, Vol. 72, No. 23, 2007 8743

Boga et al.
SCHEME 8a
Wheland complex 6a together with those of 1,3,5-tris(N,N-
morpholinyl)benzene (2).
While the reaction of Scheme 10 is complete in about 10
min, the reaction between 6a and 2 did not produce a similar
exchange: piperidinyl derivative 1 replaces morpholinyl deriva-
tive 2 because it is the more powerful electron-donor substrate,15
but 2 is not able to replace 1, at least under the present
experimental conditions.
4. Behavior of Compounds 8H and 9H. The results
described above, in particular the transfer of the diazonium
moiety reported in Scheme 3, induced us to investigate the
behavior of the final products 8Ha-c and 9Ha-c, in order to
have information about the reversibility of the last step regarding
the re-aromatization of the Wheland intermediate to the final
product of the diazo-coupling reaction.
Compounds 8Ha and 9Ha, prepared according to the reported
procedure,12 react (in CD3CN at - 30 °C) with 1 equiv of the
diazonium salts 4 or 5 affording “mixed” (unsymmetrical)
disubstituted products 17, 18, 20, and 21 (Scheme 11). Disub-
stituted compounds 10 and 17-21 can also be prepared and
isolated, in almost quantitative yields (more than 90%), as
reported in the Experimental Section. Attempts to obtain 17,
18, 20, and 21 from 8Hb,c or 9Hb,c by adding the diazonium
salt 3 failed. The attack of the second diazonium salt occurs
only when this diazonium salts is activated by the presence of
a substituent with high electron-withdrawing power. By reac-
tions of Scheme 11, different aza moieties on the 1,3,5-tris-
(N,N-dialkylamino)benzene derivatives were introduced. It is
evident that the behavior of the compounds 8Ha-c and 9Ha-c
is different with respect to their preceding Wheland complexes
6a-c and 7a-c. In fact, from compounds 8Ha-c and 9Ha-c
it was not possible to observe the exchange reaction of the
electrophilic part.
a Isomers 14a, 14b, 16Ha, and 16Hb were formed in low amount and
they bear diazonium moiety in the ortho position with respect to the
pyrrolidinic ring.
Since the second electrophilic reagent (bearing the nitro
group) is bonded to the same carbon atom as the first one, we
can conclude that the pathway represented in Scheme 6 is
unlikely to illustrate the exchanges reported above.
A third reaction pathway should be the “ipso” exchange of
the electrophilic reagent, which is supported by literature
reports,14 as represented in Scheme 9.
The “ipso” substitution pathway via the ionic reaction of
Scheme 9 is unlikely because the final product of the azocou-
pling reaction P with a second electrophilic reagent does not
give any exchange reaction, but a second attack (see the
discussion of Scheme 11) takes place. In conclusion, our data
strongly support the pathway indicated in Scheme 7 involving
the starting aromatic substrate and the electrophilic reagent in
an equilibrium forming the Wheland complex.
When compounds 20 and 21 were dissolved in CD
3CN, at
1
25 °C, without other added substances, their H NMR spectra
showed, over a very long time, partial disappearance of the
related signals, and appearance of the signals of 9Hb and 9Hc
together with the signals of the diazonium salt 3 (50% of
conversion was reached in 4 months for compound 20, and in
about 1.5 months for 21), as depicted in Scheme 12. No signals
related to diazonium salts 4 and 5 were observed: from 20 or
21 the departure of 3 (p-methoxydiazonium salt) is preferred
to the expulsion of the more powerful electrophilic reagents 4
or 5. Piperidyl cations 17 and 18 showed similar direct evidence
of spontaneous departure of diazonium salts.
3. Replacement of the Nucleophilic Moiety on a Wheland
Complex. On the basis of the reported results, with the aim of
investigating the possible exchange of the nucleophilic part of
the Wheland complexes, we prepared (in the NMR tube) a
solution of the Wheland complex 7a (by adding, at -30 °C, a
solution in CD3CN of 1,3,5-tris(N,N-morpholinyl)benzene (2)
to a solution of 4-methoxybenzenediazonium salt 3). When the
spectrum revealed complete formation of complex 7a, a solution
of 1,3,5-tris(N,N-piperidinyl)benzene (1) (in CD3CN at -30 °C,
Derivatives 10 and 19 present interesting behaviors: when
they are dissolved in CD3CN at -30 °C, directly in the NMR
1
probe tube, after about 3 days, the H NMR spectrum of the
reaction mixture shows the contemporaneous presence of the
salt 9Hb and of p-nitrobenzenediazonium salt 4, in a 30% ratio
with starting compound 19, as reported in Scheme 12. Com-
pound 10 (at 25 °C) is also not stable in a solution of CD3CN
and produces a complicated mixture of reaction products which
are under investigation.
The protonation center of salts 8H, 9H, 10, and 17-21 may
be discussed (elucidated) on the basis of the NMR data.
Protonation of 1,3,5-tris(N,N-dialkylamino)benzene derivatives
is a problem deserving further investigation. 1H and 13C NMR
spectral data indicate that the protons of salts reported here
1
in an equimolar amount with 7a) was added. The H NMR
spectrum of the obtained solution, recorded immediately after
the addition of 1, showed the disappearance of signals related
to 7a and the concomitant appearance of those related to
(14) (a) Perrin, C. L. J. Org. Chem. 1971, 36, 420-425. (b) Perrin, C.
L.; Skinner, G. A. J. Am. Chem. Soc. 1971, 93, 3389-3394. (c) Fischer, P.
B.; Zollinger, H. HelV. Chim. Acta 1972, 55, 2139-2146. (d) Bunce, N. J.
J. Chem. Soc., Perkin Trans. 1 1974, 942-944. (e) Arnold, D. P.; Johnson,
A. W.; Winter, M. J. Chem. Soc., Chem. Commun. 1976, 796-797. (f)
Moodie, R. B.; Schofield, K. Acc. Chem. Res. 1976, 9, 287-292.
(15) Knoche, W.; Sachs, W.; Vogel, S. Bull. Soc. Chim. Fr. 1988, 377-
382.
8744 J. Org. Chem., Vol. 72, No. 23, 2007

Reactions of Aromatic Substrates and Diazonium Salts
SCHEME 9
SCHEME 10
SCHEME 12
been discussed in the literature for other substrates.15,16 In the
present case this shift is the keystone of the reversibility from
final products of the diazo-coupling reaction to Wheland
intermediates. In fact, the return-back from compounds 17-21
to 8Hb,c and 9Hb,c, depicted in Scheme 12, implies the
formation of a Wheland complex bearing both the hydrogen
atom and the leaving benzendiazonium moiety on the same sp3
carbon atom. Once the Wheland complex has been formed, the
departure of the diazonium salt producing 8Hb,c or 9Hb,c is a
reasonably probable process.
SCHEME 11
Conclusions
It is worthy of consideration that when the reactivity of
reagents is stressed as in this case (the 1,3,5-tris(N,N-dialkyl-
amino)benzene system may be named a “carbon super nucleo-
philic reagent”) some aspects of the studied reactions are
enhanced and grow into manifest effects and behaviors which
are lacking in more usual, less activated systems. And this is
the case.
The main points arising from the reported data may be
summarized as follows.
(i) The formation and destruction of the double attack product
10 (arising from reaction of nitrodiazonium salt 4 on tris(N,N-
piperidyl)benzene 1, see Scheme 3) and the behavior of the
disubstituted compounds 19-21 (see Scheme 12), involving the
departure of a diazonium salt from an azo compound, clearly
indicates the complete reversibility of the process involving the
second attack of the diazonium salt.
probably participate in a multicentered interaction between two
nitrogen atoms, as represented in compound 22.
(ii) Scheme 12 indicates that from 20 and 21 the less powerful
electrophilic reagent 3 (bearing a methoxy substituent) is more
(16) (a) Effenberger, F.; Niess, R. Angew. Chem., Int. Ed. 1967, 6, 10674.
(b) Knoche, W.; Shoelle, W. W.; Schoma¨cker, R.; Vogel, S. J. Am. Chem.
Soc. 1988, 110, 7484-7489. (c) Sachs, W.; Knoche, W.; Herrmann, C. J.
Chem. Soc., Perkin Trans. 2 1991, 701-710.
It is possible that a proton shift from nitrogen atoms to a
carbon atom of aromatic ring occurs; this possibility has already
J. Org. Chem, Vol. 72, No. 23, 2007 8745

Boga et al.
(CH2), 67.7 (CH2), 68.0 (CH2), 94.5 (CH), 117.5 (CH), 126.4, 126.8
(CH), 145.9, 147.2, 156.7, 163.3.
easily lost than the more powerful electrophilic reagents 4 and
5 (with a nitro and a bromo substituent, respectively). These
findings, even if the number of electrophilic reagents is not large,
suggest the possibility of drawing an “electrofugality” scale.
(iii) In agreement with the pathway depicted in Scheme 7,
the data of Table 1 and the use of 4-[3-morpholino-5(1-
pirrolidinyl)phenyl]morpholine (12) strongly indicate that the
displacement of the methoxy-substituted diazonium cation by
the more powerful electrophilic reagent (nitro- and bromo-
substituted diazonium salt, as well as DNFB) occurs at the same
carbon atom in two subsequent steps. Consequently, the
displacement of diazonium cation from the Wheland complex
is an easy process when the entering electrophile is a more
powerful reagent than the leaving electrophile. In the same way,
the more powerful nucleophilic reagent, 1,3,5-tris(N-piperidi-
nyl)benzene (1), replaces the morpholino derivative 2.
(iv) Even if the possibility of having an “ipso” attack of the
second diazonium salt on the final azo coupling products
(Scheme 9) cannot be completely ruled out, the lack of exchange
reaction of diazonium salt from 8H and 9H (which react as
depicted in Scheme 11) indicates this pathway as unlikely.
In conclusion, the results reported here are a clear instance
of the reversibility of an electrophilic aromatic substitution
reaction. Our data strongly favor the reversibility of these
reactions, and we emphasize that this is the first instance of the
complete reversibility of an azo-coupling reaction. The systems
and the reactions reported here are a particular piece of the
electrophilic aromatic substitution reaction. The attempt to
generalize the observation reported here to the whole SEAr
reactions may be justified. In fact, the usual experimental
conditions of SEAr reactions involve several types of bases,
exciting the base catalysis on the proton abstraction, which
became a fast step.
Preparation of 4,4′-(5-pyrrolidin-1-yl-1,3-phenylene)dimor-
pholine (12). An autoclave was charged with 1,3,5-trichlorobenzene
(1.8 g, 10 mmol), pyrrolidine (2.5 mL, 30 mmol), potassium tert-
butoxide (3.4 g, 30 mmol), and dry toluene (5 mL). The autoclave
was seeled and the mixture was magnetically stirred at 120 °C.
After 24 h the reaction mixture was allowed to stand, then treated
with water to dissolve the salts. The organic layer was collected,
then the aqueous layer was extracted with dichloromethane. The
organic layers were dried over MgSO4. After filtration and
concentration in vacuo, 1-(3,5-dichlorophenyl)pyrrolidine was
isolated from the residue by flash chromatography (petroleum light/
diethyl ether from 99/1 until 90/10) as a white solid (46% yield):
1
mp 73.1-73.3 °C; H NMR (CDCl3, 300 MHz) δ 1.98-2.02 (m,
4 H), 3.22-3.25 (m, 4 H), 6.38 (d, 2 H, J ) 1.7 Hz), 6.60 (t, 1 H,
J ) 1.7 Hz); 13C NMR (CDCl3, 75.56 MHz) δ 25.4, 47.6, 109.8,
114.9, 135.3, 149.1; MS (EI, m/e, %) 214 (M+, 100), 187 (6), 172
(12), 159 (28), 145 (13). HRMS calcd for C10H11Cl2N 215.02685,
found 215.02690. Anal. Calcd for C10H11Cl2N: C, 55.58; H, 5.13.
Found: C, 55.55; H, 5.15. From the reaction mixture two other
new products were separated and characterized, whose structure
was unequivocally assigned by Nuclear Overhauser Effect experi-
ments. 1,1′-(4-Chloro-1,3-phenylene)dipyrrolidine: pale yellow
1
oil; H NMR (CDCl3, 400 MHz) δ 1.90-1.97 (m, 4 H), 1.97-
2.03 (m, 4 H), 3.22-3.30 (m, 4 H), 3.34-3.41 (m, 4 H), 6.03 (dd,
1 H, J ) 8.5, 2.9 Hz), 6.06 (d, 1 H, J ) 2.9 Hz), 7.11 (d, 1 H, J
) 8.5 Hz); 13C NMR (CDCl3, 100.56 MHz) δ 25.0, 25.5, 47.7,
50.9, 100.5, 104.4, 110.7, 131.3, 147.3, 147.5; MS (EI, m/e, %)
250 (M+, 100), 221 (6), 207 (9), 194 (11), 152 (4); HRMS calcd
for C14H19ClN2 250.12368, found 250.12370. Anal. Calcd for
C14H19ClN2: C, 67.05; H, 7.64. Found: C, 67.09; H, 7.67. 1,1′-
(2-Chloro-1,4-phenylene)dipyrrolidine: pale yellow oil; 1H NMR
(CDCl3, 400 MHz) δ 1.89-1.95 (m, 4 H), 1.95-2.02 (m, 4 H),
3.11-3.19 (m, 4 H), 3.20-3.23 (m, 4 H), 6.41 (dd, 1 H, J ) 2.7,
8.6 Hz), 6.61 (d, 1 H, J ) 2.7 Hz), 6.95 (d, 1 H, J ) 8.6 Hz); 13
C
Experimental Section
NMR (CDCl3, 100.56 MHz) δ 24.3, 25.4, 47.9, 51.5, 110.5, 113.8,
119.4, 127.8, 136.7, 144.1; MS (EI, m/e, %) 250 (M+, 100), 215
(46), 207 (12), 194 (5), 185 (15), 159 (4), 145 (6), 125 (8); HRMS
calcd for C14H19ClN2 250.12368, found 250.12367. Anal. Calcd
for C14H19ClN2: C, 67.05; H, 7.64. Found: C, 67.06; H, 7.66.
1-(3,5-Dichlorophenyl)pyrrolidine (0.7 g, 3 mmol), morpholine
(1.0 mL, 12 mmol), potassium tert-butoxide (1.5 g, 12 mmol), and
toluene (5 mL) were introduced in an autoclave. The vessel was
seeled and the mixture was magnetically stirred at 200 °C. After
72 h the reaction mixture was allowed to stand, then treated with
water until the salts were dissolved. The organic layer was collected,
then the aqueous layer was extracted with dichloromethane. The
organic layers were dried over MgSO4. After filtration and
concentration in vacuo, 4,4′-(5-pyrrolidin-1-yl-1,3-phenylene)-
dimorpholine (12) was purified by flash chromatography (petro-
leum light/diethyl ether from 99/1 until 90/10) and obtained in 75%
yield as a white solid: mp 247.8-248.2 °C, 1H NMR (CDCl3, 300
MHz) δ 1.95-2.00 (m, 4 H), 3.13-3.16 (m, 8 H), 3.26-3.30 (m,
4 H), 3.83-3.86 (m, 8 H), 5.73 (d, 2 H, J ) 1.9 Hz), 5.89 (t, 1 H,
J) 1.9 Hz); 13C NMR (CDCl3, 75 MHz) δ 25.4, 47.7, 50.1, 67.1,
93.1, 93.4, 149.4, 153.4; MS (EI, m/e, %) 317 (M+, 100), 288 (11),
274 (10), 260 (59), 200 (14), 158 (13), 145 (6), 100 (13); HRMS
calcd for C18H27N3O2 317.21033, found 317.21035. Anal. Calcd
for C18H27N3O2: C, 68.11; H, 8.57. Found: C, 68.08; H, 8.60.
Formation and behavior of Wheland Complex 13a: General
Procedure. To a solution of compound 12 (0.010 g, 0.0315 mmol),
prepared in CD3CN (0.5 mL) at -30 °C directly in a NMR tube,
was added a solution containing diazonium salt 3 (0.0315 mmol in
0.5 mL of CD3CN), cooled at -30 °C. The reaction mixture was
monitored each 5 min, until its 1H NMR spectrum showed complete
disappearance of signals related to compound 3, and concomitant
Compounds 1 and 2 were prepared as reported in ref 12.
Diazonium salts 3-5 are commercially available. Preparation and
characterization data of complexes 6a-c, 7a-c, and 11, as well
as salts 8Ha-c and 9Ha-c, has been previously reported.12,13
Preparation of Compounds 10 and 19. To a magnetically
stirred solution (0.092 mmol in 2 mL of CH3CN) of 1,1′,1′′-
benzene-1,3,5-triyltripiperidine (1) (or 4,4′,4′′-benzene-1,3,5-triyl-
trimorpholine, 2), cooled at -30 °C, was added arenediazonium
salt 4 (0.184 mmol). Immediately the color of the obtained solution
became yellow. After 20 min a coral-red solid precipitated. After
filtration compound 10 (or 19, tile-red solid) was isolated as coral
red solid in 90% yield (85% for 16). Compounds 10 and 19 can be
obtained also by addition of an equimolar amount of diazonium
salt 4 to a cooled (-30 °C) solution in acetonitrile of compound
8Hb or 9Hb, respectively.
1,1′-{2,4-Bis[(4-nitrophenyl)diazenyl]-5-piperidin-1-yl-1,3-
phenylene}dipiperidinium ditetrafluoroborate (10): mp 128.8-
132.4 °C dec; 1H NMR (CD3NO2, 400 MHz, 25 °C) δ 1.50-2.80
(m, 18 H), 3.50-4.80 (m, 12 H), 6.38 (br s, 1 H), 7.50 (d, 4 H, J
) 9.3 Hz), 8.20 (d, 4 H, J ) 9.3 Hz), 10.24 (br s, 2 H); 13C NMR
(CD3NO2, 100.56 MHz, -30 °C) δ 18.4 (CH2), 18.9 (CH2), 20.9
(CH2), 22.5 (CH2), 23.2 (CH2), 45.4 (CH2), 49.4 (CH2), 55.1 (CH2),
88.5 (CH), 111.6 (CH), 121.3 (CH),122.3, 139.9, 142.0, 150.8, 157.3.
3-{3-Morpholin-4-ium-4-yl-5-morpholin-4-yl-2,6-bis[(4-nitro-
phenyl)diazenyl]phenyl}-1,3-oxazinan-3-ium ditetrafluoroborate
1
(19): mp 142.8-147.9 °C dec; H NMR (CD3CN, 300 MHz, 25
°C) δ 2.02-2.42 (m, 8 H), 3.82-4.20 (m, 16 H), 6.25 (s, 1 H),
7.68 (d, 4 H, J ) 9.1 Hz), 8.37(d, 4 H, J ) 9.1 Hz), 10.22 (br s,
1
2 H); H NMR (CD3NO2, 400 MHz, 25 °C) δ 2.10-2.45 (m, 12
H), 3.65-4.75 (m, 12 H), 6.40 (s, 1 H), 7.60 (d, 4 H, J ) 9.3 Hz),
8.26 (d, 4 H, J ) 9.3 Hz), 10.44 (br s, 2 H); 13C NMR (CD3NO2,
150.56 MHz, -30 °C) δ 50.1 (CH2), 53.8 (CH2), 59.3 (CH2), 66.7
1
appearance of signals of the Wheland complex 13a: H NMR (CD3-
CN, 300 MHz, -30 °C) δ 1.97-2.40 (m, 4 H), 3.18-3.88 (m, 20
8746 J. Org. Chem., Vol. 72, No. 23, 2007

Reactions of Aromatic Substrates and Diazonium Salts
H), 3.89 (s, 3 H), 5.32 (s, 2 H), 6.42 (s, 1 H), 7.08 (d, 2 H, J ) 8.8
Hz), 7.72 (d, 2 H, J ) 8.8 Hz). Once complex 13a was completely
formed, a solution of salt 4 (0.0315 mmol in 0.5 mL of CD3CN),
cooled at - 30 °C, was added. Immediately, the spectrum showed
disappearance of signals related to the p-methoxyphenyl moiety of
complex 13a, with concomitant appearance both of signals belong-
ing to salt 3, and to those of complex 13b: 1H NMR (CD3CN, 300
MHz, -30 °C) δ ) 1.98-2.10 (m, 8 H), 3.40-4.00 (m, 16 H),
5.35 (s, 2 H), 6.69 (s, 1 H), 7.89 (d, 2 H, J ) 8.7 Hz), 8.40 (d, 2
H, J ) 8.7 Hz).
as reported in ref 12, cooled at -30 °C, was added 0.092 mmol of
arenediazonium tetrafluoborate 4 or 5. Immediately the solution
assumed a yellow color. After magnetic stirring for 20 min the
color turned red. After removal of the solvent in vacuo, the crude
product was dissolved in 2 mL of CH2Cl2 and the compounds 17
or 18, or 20, or 21 were precipitated by adding Et2O. The products
17 or 18, or 20, or 21 were isolated as solids in 80-90% yield and
crystallized from CH2Cl2 and n-hexane.
1,1′-{4-[(4-Methoxyphenyl)diazenyl]-2-[(4-nitrophenyl)di-
azenyl]-5-piperidin-1-yl-1,3-phenylene}dipiperidinium ditet-
rafluoroborate (17): red solid, yield 90%, mp 135.2-148.3 °C
1
The H NMR spectrum containing complex 13a showed the
1
dec; H NMR (CD3CN, 400 MHz, 25 °C) δ 1.7-2.46 (m, 18 H),
presence of other signals, ascribed to complex 14a, obtained by
attack of diazonium salt 3 to 12 in the ortho-position with respect
to the pyrrolidinic ring; the relative ratio of the sp3 CH signals of
the σ-complexes revealed the presence of complex 14a in minor
amount with respect to 13a. Complex 14a: 1H NMR (CD3CN, 300
MHz, -30 °C) δ 1.95-2.40 (m, 4 H), 2.90-3.98 (m, 20 H), 3.84
(s, 3 H), 5.20 (s, 1 H), 5.49 (s, 1 H), 6.26 (s, 1 H), 7.02 (d, 2 H, J
) 8.9 Hz), 7.42 (d, 2 H, J ) 8.9 Hz). After addition of diazonium
salt 4, the spectrum showed the presence of both complex 13b and
complex 14b, allowing from the analogous parallel reaction
exchange on compounds 14a. Complex 14b: 1H NMR (CD3CN,
300 MHz, -30 °C) δ 1.98-2.25 (m, 4 H), 2.80-4.05 (m, 20 H),
5.23 (s, 1 H), 5.53 (s, 1 H), 6.50 (s, 1 H), 7.50 (d, 2 H, J ) 8.7
Hz), 8.29 (d, 2 H, J ) 8.7 Hz).
Solutions of compounds 13a (containing 14a) and 13b (contain-
ing 14b) are not stable and spontaneously formed salts 15Ha and
15Hb (and related 16Ha and 16Hb), as previously reported for
complexes 6a-c and 7a-c.10 Compounds 15Ha and 15Hb can be
isolated also by precipitation from their reaction mixture according
to the procedure previously reported for obtaining compounds
8Ha-c and 9Ha-c.12 Chemicophysical data of compounds 15Ha
and 15Hb, together with those of the corresponding minor isomers
16Ha and 16Hb, are as follows:
4,4′-{2-[(4-Methoxyphenyl)diazenyl]-5-pyrrolidin-1-yl-1,3-
phenylene}dimorpholine‚HBF4 (15Ha): 95% yield, red solid,
impure of its isomer 16Ha: 1H NMR (CDCl3, 300 MHz, 25 °C) δ
1.99-2.23 (m, 4 H), 2.95-3.16 (m, 2 H), 3.19-3.36 (m, 2 H),
3.83 (s, 3 H), 3.53-4.17 (m, 16 H), 5.60 (d, 1 H, J ) 1.8 Hz),
6.01(d, 1 H, J ) 1.8 Hz), 6.95 (d, 2 H, J ) 9.1 Hz), 7.28 (d, 2 H,
J ) 9.1 Hz), 12.41 (s, 1 H); 13C NMR (CDCl3, 100.56 MHz, -30
°C) δ 25.0, 25.1, 47.8, 50.1, 50.9, 51.1, 51.3, 55.7, 66.4, 66.5, 66.7,
93.6, 100.1, 115.5, 117.1, 123.4, 135.1, 151.2, 157.1, 157.9, 159.3.
Anal. Calcd for C25H34BF4N5O3 (539.37): C, 55.67; H, 6.35.
Found: C, 55.65; H, 6.37. ES+: 452. ES-: 87. 4,4′-{4-[(4-
Methoxyphenyl)diazenyl]-5-pyrrolidin-1-yl-1,3-phenylene}di-
morpholine‚HBF4 (16Ha): 1H NMR (CDCl3, 300 MHz, 25 °C) δ
1.99-2.23 (m, 4 H), 2.95-3.16 (m, 2 H), 3.19-3.36 (m, 4 H),
3.53-4.17 (m, 16 H), 3.83 (s, 3H), 5.55 (d, 1 H, J ) 1.9 Hz), 6.17
(d, 1 H, J ) 1.9 Hz), 6.95 (d, 2 H, J ) 9.1 Hz), 7.24 (d, 2 H, J )
8.9 Hz), 12.73 (br s, 1 H).
3.35-4.50 (m, 12 H), 3.87 (s, 3 H), 6.22 (s, 1 H), 7.07 (d, 2 H, J
) 9.02 Hz), 7.51 (d, 2 H, J ) 9.02 Hz), 7.63 (d, 2 H, J ) 9.2 Hz),
8.33 (d, 2 H, J ) 9.2 Hz), 9.94 (s, 1 H), 10.02 (s, 1 H); 13C NMR
(CD3CN, 100.56 MHz, -30 °C) δ 22.5, 22.6, 22.8, 24.6, 24.7, 26.1,
26.6 (2 signals overlapped), 26.9, 49.1, 49.5, 53.0, 53.4, 54.9, 58.1,
58.2, 91.4, 114.4, 115.3, 117.9, 121.1, 125.3, 126.6, 134.3, 143.5,
146.2, 154.8, 155.5, 157.9, 161.7. Anal. Calcd for C34H44B2F8N8O3
(786.37): C, 51.93; H, 5.64. Found: C, 51.99; H, 5.62.
1,1′-{2-[(4-Bromophenyl)diazenyl]-4-[(4-methoxyphenyl)di-
azenyl]-5-piperidin-1-yl-1,3-phenylene}dipiperidinium ditet-
rafluoroborate (18): red solid, yield 80%, mp 130.2-140.4 °C
dec; 1H NMR (CD3CN, 400 MHz, 25 °C) δ 1.63-2.07 (m, 18 H),
3.63-3.97 (m, 12 H), 3.86 (s, 3 H), 6.24 (s, 1 H), 7.05 (d, 2 H, J
) 8.8 Hz), 7.42 (d, 2 H, J ) 8.8 Hz), 7.51 (d, 2 H, J ) 9.1 Hz),
7.64 (d, 2 H, J ) 9.1 Hz), 9.80 (br s, 1 H), 9.92 (br s, 1 H); 13C
NMR (CD3CN, 100.56 MHz, -30 °C) δ 22.1, 22.8, 22.9, 24.3 (2
signals overlapped), 26.0, 26.3, 26.4, 27.1, 48.6, 49.4, 53.1, 53.3,
55.4, 57.5, 58.3, 92.6, 114.9, 115.3, 117.9, 118.3, 118.9, 121.7,
132.5, 135.7, 140.8, 155.7, 156.0, 158.5, 162.4. Anal. Calcd for
C34H44B2BrF8N7O (820.27): C, 49.78; H, 5.41. Found: C, 49.73;
H, 5.40.
4,4′-{4-[(4-Methoxyphenyl)diazenyl]-5-morpholin-4-yl-2-[(4-
nitrophenyl)diazenyl]-1,3-phenylene}bismorpholin-4-ium ditet-
rafluoroborate (20): tile red solid, yield 88%, mp 139.9-154.8
1
°C dec; H NMR (CD3CN, 400 MHz, 25 °C) δ 2.1-2.4 (m, 4H),
3.40-4.16 (m, 16H), 3.95 (s, 3H), 4.21-4.77 (m, 4H), 6.24 (s,
1H), 7.10 (d, 2H, J ) 9.16 Hz), 7.54 (d, 2H, J ) 9.16 Hz), 7.65
(d, 2H, J ) 9.16 Hz), 8.35 (d, 2H, J ) 9.16 Hz), 10.15 (br s, 1H),
10.20 (br s, 1H); 13C NMR (CD3CN, 100.56 MHz, -30 °C) δ 48.4,
48.7, 49.3, 49.9, 55.5, 57.4 (2 signals overlap), 66.2, 66.4, 65.7,
66.7 (2 signals overlap), 66.8, 92.9, 115.0, 116.4, 118.8, 120.9,
125.6, 126.0, 135.7, 144.7, 146.4, 156.0, 156.8, 159.0, 162.7. Anal.
Calcd for C31H38B2F8N8O6 (792.29): C, 46.99; H, 4.83.Found: C,
47.02; H, 4.84.
4,4′-{2-[(E)-(4-Bromophenyl)diazenyl]-4-[(E)-(4-methoxyphen-
yl)diazenyl]-5-morpholin-4-yl-1,3-phenylene}bismorpholin-4-ium
ditetrafluoroborate (21): tile red solid, yield 85%, mp 142.3-
1
162.5 °C dec; H NMR (CD3CN, 300 MHz, 25 °C) δ 2.23-2.33
(m, 4H), 3.60-4.13 (m, 16H), 3.93 (s, 3H), 4.20-4.41 (m, 4H),
6.22 (s, 1H), 7.11 (d, 2H, J ) 9.11 Hz), 7.50 (d, 2H, J ) 9.11 Hz),
7.61 (d, 2H, J ) 9.11 Hz), 7.66 (d, 2H, J ) 9.11 Hz), 10.05 (br s,
1H), 10.21 (br s, 1H); 13C NMR (CD3CN, 75.56 MHz, -30 °C) δ
47.5, 47.8, 50.0, 52.1, 55.0, 57.0, 57.2, 65.1, 65.3, 65.8, 66.1(2
signals overlap), 66.4, 91.8, 114.4, 116.4, 117.9, 118.1, 120.7, 122.9,
132.3, 134.2, 140.3, 155.7, 156.1, 158.1, 162.4. Anal. Calcd for
C31H38B2BrF8N7O4 (826.19): C, 45.07; H, 4.64. Found: C, 46.00;
H, 4.63.
4,4′-{2-[(4-Nitrophenyl)diazenyl]-5-pyrrolidin-1-yl-1,3-phen-
ylene}dimorpholine‚HBF4 (15Hb): 95% yield, red solid, impure
of its isomer 16Hb: 1H NMR (CD3CN, 400 MHz, 25 °C) δ 2.02-
2.11 (m, 4 H), 2.88-3.10 (m, 2 H), 3.21-3.41 (m, 2 H), 3.56-
4.16 (m, 16 H), 5.66 (d, 1 H, J ) 2.0 Hz), 5.93 (d, 1 H, J ) 2.0
Hz), 7.54 (d, 2 H, J ) 9.0 Hz), 8.31 (d, 2 H, J ) 9.0 Hz), 11.87
(br s, 1 H); 13C NMR (CD3CN, 100.56 MHz, -30 °C) δ 24.4,
24.6, 48.1, 50.3, 50.4, 50.6, 50.7, 65.7, 65.8, 66.3, 92.1, 99.4, 115.2,
125.7, 128.2, 143.5, 147.2, 150.9, 157.8, 158.9. Anal. Calcd for
C24H31BF4N6O4 (554.35): C, 52.00; H, 5.64. Found: C, 51.97; H,
5.37. ES+: 467. ES-: 87. 4,4′-{4-[(4-Nitrophenyl)diazenyl]-5-
Acknowledgment. This work was supported by funds from
a fellowship entitled to the memory of Alessandro Zucchelli
and by ALMA MATER STUDIORUM-Universita` di Bologna
(ex-60% MIUR).
Supporting Information Available: General experimental
details and copies of 1H and 13C NMR spectra of new compounds.
This material is available free of charge via the Internet at
http://pubs.acs.org.
1
pyrrolidin-1-yl-1,3-phenylene}dimorpholine‚HBF4 (16Hb): H
NMR (CD3CN, 400 MHz, 25 °C) δ 2.02-2.11 (m, 4 H), 2.88-
3.10 (m, 2 H), 3.21-3.41 (m, 2 H), 3.56-4.16 (m, 16 H), 5.58 (d,
1 H, J ) 2.4 Hz), 6.09 (d, 1 H, J ) 2.4 Hz), 7.53 (d, 2 H, J ) 8.8
Hz), 8.30 (d, 2 H, J ) 8.9 Hz), 12.28 (br s, 1 H).
Preparation of Compounds 17, 18, 20, and 21. To a solution
of salt 8Ha (or 9Ha) (0.092 mmol in 2 mL of CH3CN), prepared
JO071111K
J. Org. Chem, Vol. 72, No. 23, 2007 8747