On the amination of tetraazafulvalenes

Article abstract of DOI:10.1055/s-2001-15153

The palladium catalyzed amination of tetraazafulvalenes is described. Starting from either the tetraalkylated compounds 7 or their vinylogous derivatives 8, substitution of the aryl bromide by different amines was realized. The synthesis of compounds whic

Full text of DOI:10.1055/s-2001-15153

1188
LETTER
On the Amination of Tetraazafulvalenes
Christian Käpplinger, Rainer Beckert*
Institut für Organische und Makromolekulare Chemie, Friedrich-Schiller-Universität Jena, Humboldtstrasse 10, 07743 Jena, Germany
Fax +49(3641)948212; E-mail: c6bera@rz.uni-jena.de
Received 25 April 2001
group. However, in our first experiments, no substitution
Abstract: The palladium catalyzed amination of tetraazafulvalenes
reaction could be observed. This is probably due to the
fact that the vicinal diamino substructure in the educts 1
and 2 forms a new complex with the metal which is then
is described. Starting from either the tetraalkylated compounds 7 or
their vinylogous derivatives 8, substitution of the aryl bromide by
different amines was realized. The synthesis of compounds which
possess four primary amino groups as well as four hydrazino resi- inactivated and unable to participate in the catalytic cycle.
dues by employing a one-pot, two-step method is also described.
The solution to this problem results in a previous cycliza-
Bichromophores are accessible as demonstrated by the introduction
tion of 1 with orthoformate2 leading to a 1:1 syn/anti mix-
ture of compound 5. Initial studies using morpholine or
of the phenoxazine system into tetraazafulvalenes.
Key words: aminations, arenes, cross-coupling, heterocycles, pal-
diphenylketimine in the presence of a palladium catalyst
ladium, tetraazafulvalenes
(Pd2dba3/rac-BINAP) confirmed this. The amination of 5
to products 6a and 6b was then easily realized. It is note-
worthy to mention that in the case of the conversion of 5
Numerous syntheses of 1,4,5,8-tetraazafulvalenes of type
to 6a,b only cesium carbonate as a weak base led to an
1 and 2 have been previously described.1-4 Due to their re-
amino transfer reaction whereas sodium tert-butoxide and
dox properties as well as their multifunctionalities, these
electron deficient heterofulvalenes offer the possibility of
constructing functional dyes and dentritic structures. In
LiHMDS were inactive. Both of the new amino deriva-
tives 6a,b could be isolated and structurally characterized.
However, due to their poor solubility, a further derivatiza-
particular, the introduction of amino groups into the aro-
tion seemed to be useless. Another pathway to derivatives
matic residues of tetraazafulvalenes should be of interest.
showing a good solubility and unable to complex the met-
Protonation and alkylation reactions should thus afford
water soluble derivatives. In addition, the auxochromic
NR2-substructures should lead to a bathochromic shift of
the long wavelength absorption maxima of compounds 1
al is the alkylation of heterofulvalenes 1 and 2.2 Thus,
treatment of 1 and 2, with ethyl iodide in the presence of
a base lead to the tetraalkylated compounds 7 and 8, re-
spectively in a smooth reaction (Scheme 2). Subsequent-
ly, 7 and 8 were converted into different amino aryl
and 2.
All attempts to synthesize derivatives which possess
amino groups (1, 2 with Ar = 4-R2NC6H4) at the aromatic
residues have failed to date because the corresponding
educts 3 and 4 are not accessible. Reduction of the less
soluble 4-nitro derivatives of compounds 1 and 2
(Ar = 4-O2NC6H4) did not give the desired amino deriva-
tives either. We now report that metal catalyzed amination
allows the synthesis of these compounds. Thus, under
palladium5 or nickel catalysis6, aromatic halogen atoms in
1 and 2 can be replaced by amino groups under mild con-
ditions. Encouraged by the results reported in the litera-
ture, we started from easily accessible tetraazafulvalenes
1 and 2 bearing a bromine atom in para position of the aryl
heterofulvalenes 9, 10 (Scheme 3).
The direct metal catalyzed substitution of bromine by am-
monia leading to primary amino groups was not success-
ful.7 We therefore employed the coupling reaction of
bromo derivatives 7 and 8 with benzophenone imine.8 Fi-
nal treatment of the amination products 9d,10d with hy-
drochloric acid formed the desired primary amines 9h,10h
under cleavage of benzophenone. In an analogous man-
ner, the hydrazino derivatives 9e,10e were synthesized via
the hydrazones 9i,10i. Moreover, with the substitution of
bromine by the phenoxazine fragment to 9g,10g, an easy
access to bichromophoric systems is obtained.9
Scheme 1
Synlett 2001, No. 7, 1188–1190 ISSN 0936-5214 © Thieme Stuttgart · New York

LETTER
On the Amination of Tetraazafulvalenes
1189
Scheme 2
Scheme 3
In the UV/Vis spectra of derivatives 9a-c and 10a-c, the In addition to the typical absorption for tetraazafulvalenes
longest wavelength absorption maxima are bathochromi- at about 570 nm, the phenoxazine dye in 9g is character-
cally shifted only about 10 nm as compared to the haloge- ized by a second strong absorption at 635 nm.
nated educts. A much stronger influence was obtained
with the diphenylketimine substructure (9d: max = 586
nm, 10d: max = 606 nm) which was further increased by
Acknowledgement
This work was supported by the Deutsche Forschungsgemeinschaft,
Roche Diagnostics GmbH and the Fonds der Chemischen Industrie
cleavage of benzophenone: the hydrochloride of 9h ab-
sorbs at max = 632 nm and that of 10h at max = 658 nm.
Synlett 2001, No. 7, 1188–1190 ISSN 0936-5214 © Thieme Stuttgart · New York

1190
C. Käpplinger, R. Beckert
LETTER
(q, 4 H), 3.89 (q, 4 H), 3.78 (m, 16 H), 3.10 (m, 16 H), 1.21 (t,
6 H), 1.14 (t, 6 H). UV/Vis (DMSO): max (lg ) = 552 nm
(4.8). 10a: from 8 and morpholine. (82mg, 84%), mp 309 °C.
1H NMR (250 MHz, CD2Cl2): = 6.61 (m, 12 H), 6.46 (d,
4H), 6.32 (s, 2H), 3.96 (q, 4 H), 3.81 (m, 16 H), 3.67 (q, 4 H),
3.05 (m, 16 H), 1.24 (t, 6 H), 1.15 (t, 6H). 13C NMR (62 MHz,
CD2Cl2): = 149.1, 148.1, 146.8, 146.2, 144.3, 136.8, 126.1,
121.4, 116.0, 97.9, 67.4, 67.2, 51.0, 50.0, 48.9, 36.8, 13.9,
13.0. UV/Vis (DMSO): max (lg ) = 561 nm (4.9). 10b: from
8 and dioctylamine. (72 mg, 45%), mp 120 °C. MS (DCI with
water): m/z = 1592 (M+), 1522, 520, 364, 102. UV/Vis
(DMSO): max (lg ) = 566 nm (4.9). 10c: from 8 and
diphenylamine. (102 mg, 78%), mp 93 °C. 1H NMR (400
MHz, CD2Cl2): = 7.35 (m, 22 H), 7.02 (m, 18 H), 6.86 (m, 8
H), 6.47 (m, 8 H), 6.25 (s, 2 H), 3.98 (q, 4 H), 3.74 (q, 4 H),
1.29 (t, 6 H), 1.16 (t, 6 H). MS (ESI in CHCl3/MeOH): m/
z = 1303.7. 10d: from 8 and benzophenone imine. (121 mg,
89%), mp 268 °C. 1H NMR (400 MHz, CD2Cl2): = 7.72 (m,
8H), 7.45 (m, 4H), 7.39 (m, 8H), 7.29 (m, 8 H), 7.15 (m, 8 H),
7.08 (m, 4 H), 6.74 (m, 4 H), 6.53 (m, 8 H), 6.31 (m, 4 H), 6.22
(s, 2 H), 3.95 (q, 4H), 3.40 (q, 4 H), 1.17 (t, 6 H), 0.93 (t, 6 H).
13C NMR (100 MHz, CD2Cl2): = 168.1, 167.5, 148.8, 146.4,
145.9, 145.0, 140.4, 140.2, 139.9, 137.4, 136.5, 130.9, 130.8,
129.9, 129.8, 129.6, 129.4, 129.0, 128.7, 128.4, 128.3, 128.2,
125.9, 121.8, 121.5, 120.6, 97.5, 48.6, 37.1, 13.9, 13.0. UV/
Vis (DMSO); max (lg ) = 360 nm (4.4), 606 (4.7). MS (ESI
in CHCl3/MeOH); m/z = 1351.7. 10e: from 8 and
References and Notes
(1) Brandenburg, J.; Käpplinger, C.; Beckert, R. Synthesis 1996,
1302.
(2) Käpplinger, C.; Beckert, R.; Günther, W.; Görls, H. Liebigs
Ann./Recueil 1997, 617.
(3) Käpplinger, C.; Beckert, R. J. Prakt. Chem. 1998, 340, 323.
(4) Müller, D.; Beckert, R.; Görls, H. Synthesis 2001, 601.
(5) Wolfe, J. P.; Buchwald, S. L. J. Org. Chem. 2000, 65, 1144;
Hartwig, J. F.; Kawatsura, M.; Hauck, S. I.; Shaughnessy, K.
H.; Alcazar-Roman, L. M. J. Org. Chem. 1999, 64, 5575;
Beletskaya, I. P.; Bessmertnykh, A. G.; Guilard, R. Synlett
1999, 1459; Stauffer, S. R.; Lee, S.; Stambuli, J. P.; Hauck, S.
I.; Hartwig, J. F. Org. Lett. 2000, 2, 1423; Wolfe, J. P.;
Tomori, H.; Sadighi, J. P.; Yin, J.; Buchwald, S. L. J. Org.
Chem. 2000, 65, 1158.
(6) Wolfe, J. P.; Buchwald, S. L. J. Am. Chem. Soc. 1997, 119,
6054; Lipshutz, B. H.; Ueda, H. Angew. Chem. Int. Ed. 2000,
39, 4492.
(7) With these primary amines, mainly the disubstitution products
were formed even at longer reaction times.
(8) Wolfe, J. F.; Ahman, J.; Sadighi, J. P.; Singer, R.; Buchwald,
S. Tetrahedron Lett. 1997, 38, 36, 6367; Mann, G.; Hartwig,
J. F.; Driver, M.; Fernandez-Riva, C. J. Am. Chem. Soc. 1998,
120, 4, 827.
(9) Typical procedure for alkylation of tetraazafulvalenes: A
mixture of 2 (0.83 g, 1 mmol), cesium carbonate (1.62 g, 5
mmol) and ethyl iodide (0.78g, 5 mmol) in 20 mL of anhyd
DMF was heated to 50 °C for 12 h. After addition of 10 mL of
water, the precipitate was filtered off and the crude product
was purified by column chromatography (alumina, toluene/
heptane 1/1). 8: (0.61 g, 64%). 1H NMR (250 MHz, CD2Cl2):
= 7.22 (d, 4 H), 7.13 (d, 4 H), 6.67 (d, 4 H), 6.47 (s, 2 H),
6.30 (d, 4 H), 3.94 (q, 4 H), 3.43 (q, 4 H), 1.21 (t, 6 H), 1.10
(t, 6 H). UV/Vis (DMSO): max (lg ) = 557 nm (4.8). MS
(DCI with H2O): m/z = 954 (100), 951, 873, 632.
benzophenone hydrazone. (96 mg, 67%), mp 199 °C. 1H NMR
(250 MHz, CD2Cl2): = 7.56 (d, 16 H), 7.30 (m, 20 H), 7.27
(m, 10 H), 6.84 (m, 10 H), 6.47 (s, 2 H), 4.02 (q, 4 H), 3.61 (q,
4 H), 1.06 (t, 6 H), 0.86 (t, 6 H). MS (ESI in CHCl3/MeOH):
m/z = 1411.8. 10f: from 8 and 1-aminoadamantane. (33 mg,
27%), mp 132 °C. MS (DCI with water): m/z = 1232 (M+).
UV/Vis (DMSO): max (lg ) = 567 nm (4.8). 10g: from 8a and
nile blue. (30 mg, 12%), mp > 350 °C. 1H NMR (250 MHz,
CD2Cl2): = 8.43 (m, 10 H), 7.56 (m, 22 H), 7.24 (m, 42 H),
6.86 (m, 12 H), 6.4 (m, 8 H), 6.02 (s, 2 H), 4.12 (q, 4 H), 3.82
(q, 4 H), 3.21 (q, 8 H), 3.11 (q, 8 H), 1.21 (m, 24 H), 1.04 (t, 6
H), 1.01 (t, 6 H). UV/Vis (DMSO): max (lg ) = 568 nm (4.8),
638 (4.7).
The cleavage of the imine 10d or hydrazone 10e was realized
in acetone as solvent by addition of a few drops of 2 M HCl.
The precipitation was filtered off and recrystallized from
ethanol. 10h: mp 255 °C. MS (DCI with H2O): m/z = 695
(M+), 627, 503, 245, 102. UV/Vis (DMSO): max (lg ) = 658
nm (4.7). 10i: mp 265 °C. MS (DCI with H2O): m/z = 755
(M+), 687, 512, 102.
Typical procedure for amination reactions: A schlenk tube
was charged with Pd2(dba)3 (20 lmol), rac-BINAP (20 lmol),
sodium tert-butoxide (for 6a,b: cesium carbonate) (0.5
mmol), tetraazafulvalenes 5, 7 or 8 (0.1 mmol), amine (0.5
mmol) and 10 mL toluene under argon. The mixture was
heated to 100 °C with stirring until completion of the reaction
(TLC). The reaction mixture was then cooled to r.t., taken up
in diethyl ether, washed with water, dried over Na2SO4 and
evaporated in vacuo. Column chromatography of the residue
on alumina gave pure products.
Selected data for 6b: from 5 and benzophenone imine. Mp
280 °C (dec.). 1H NMR (250 MHz, CD2Cl2): = 7.78 (d, (16
H), 7.47 (m, 10 H), 7.32 (d, 16 H), 7.15 (m, 8 H), 6.85 (d, 8
H), 3.32 (q, 4 H), 1.00 (t, 6 H). MS (ESI in CHCl3/MeOH): m/
z = 1325.6. 9a: from 7 and morpholine. (71 mg, 74%), mp
318 °C. MS (ESI in CHCl3/MeOH): m/z = 949.2. 1H NMR
(250 MHz, CD2Cl2): = 7.02 (m, 8 H), 6.56 (m, 8 H), 4.52
Article Identifier:
1437-2096,E;2001,0,07,1188,1190,ftx,en;G07701ST.pdf
Synlett 2001, No. 7, 1188–1190 ISSN 0936-5214 © Thieme Stuttgart · New York