Pd-catalyzed coupling of non-activated dibromoarenes to 2,3-diaminoarenes: Formation of N,N′-dihydropyrazines

Article abstract of DOI:10.1002/chem.201303277

Accessible azaacenes: Pd-catalyzed coupling reactions between aromatic diamines and unactivated aromatic dibromides furnish N,N′- dihydrodiazapentacenes, -hexacenes, and -heptacenes (see scheme; TIPS=triisopropylsilyl). Oxidation of these products led to diazapentacenes and a diazahexacene. The existence of a diazaheptacene intermediate was proven by solving the single-crystal structure of its (4+4) dimerization product.

Full text of DOI:10.1002/chem.201303277

COMMUNICATION
DOI: 10.1002/chem.201303277
Pd-Catalyzed Coupling of Non-Activated Dibromoarenes to 2,3-
Diaminoarenes: Formation of N,N’-Dihydropyrazines
Jens U. Engelhart, Benjamin D. Lindner, Olena Tverskoy, Frank Rominger, and
Uwe H. F. Bunz*[a]
The larger azaacenes are of current interest as charge-
transport materials for electrons and holes.[1] There is
a shortage of efficient approaches towards their synthesis.[2,3]
We have previously shown that diaminoarenes, such as 6 or
10 (see Scheme 1), couple efficiently by Pd catalysis to 2,3-
dichloroquinoxaline, an activated coupling partner where
the strongly electron-accepting nature of its aromatic nu-
cleus facilitates Pd-catalyzed couplings.[4,5] Simply heating
the reaction components (6 or 10, and 2,3-dichloroquinoxa-
Figure 1. Tested catalysts and ligands for amination of ortho-dibromides.
line) in the presence of [PdACTHNUTRGNE(UNG dba)2] (dba=dibenzylideneace-
tone) and Buchwaldꢀs dialkylbiarylphosphine 2 in Hꢁnigs
base gives N,N-dihydrotetraazapentacenes and -hexacenes;
MnO2 then oxidizes the products of the coupling reaction
into the fully aromatic tetraazaacenes.[4] However, we were
never able to couple non-activated halides to substituted ar-
omatic diamines. We found it critical to tackle this problem
to access a larger range of diazacenes.[6,7] We now offer a so-
lution to this problem by demonstrating the efficient Pd-cat-
alyzed coupling of substituted 2,3-diaminonaphthalenes and
Scheme 1. Coupling of diaminoarene 6 to dichlorobenzene 7.
2,3-diaminoanthracenes
to
1,2-dibromobenzene,
1,2-
ture analysis of 8 proved its structure (see the Supporting
Information).
dichlorobenzene, 2,3-dibromonaphthalene, and 2,3-dibro-
ACHTUNGTRENNUNG
moanthracene. The resulting coupling products were trans-
formed into diazahexacene and diazaheptacene derivatives,
the latter a fleeting intermediate, which is ultimately con-
verted to its dimer.
Our initial experiments to couple diaminoarene 6 to di-
chlorobenzene 7 under previously optimized reaction condi-
tions were not successful. However, after substituting
Hꢁnigs base with NaOtBu and working under microwave
(mw) heating, in the presence of precatalyst 1a (Figure 1),
diazaacene 9 was isolated with a yield of 5% together with
a 92% yield of singly coupled product 8, which was resistant
to further reaction because the halogenated ring in com-
pound 8 is now electron rich (Scheme 1). X-ray crystal-struc-
We then investigated different reaction conditions for the
coupling of diaminoarene 10 to dibromide 11 to access de-
sired acene, 12, (Scheme 2). We found the following: 1)
Cs2CO3 is the most effective base and provides the highest
conversions. 2) Microwave-promoted reactions show higher
conversion compared to conventional heating using an oil
bath. 3) Upon testing several precatalysts (1a,[5] 1b, 4, and
5/ACTHNURGTENN[UG Pd2ACHTUNTGREN(NUNG dba)3]) the cyclometalated complex 1a, which fea-
tures a highly active Pd center, is the most efficient catalyst
for this transformation. 4) Conducting the reactions at tem-
peratures below 1208C results in low conversion. 5) THF is
the best solvent for microwave-promoted experiments, but
tends to damage the seal of the microwave vessel; dioxane
[a] Dipl. Chem. J. U. Engelhart, Dipl. Chem. B. D. Lindner, O. Tverskoy,
Dr. F. Rominger, Prof. U. H. F. Bunz
Organisch-Chemisches Institut
Ruprecht-Karls-Universitꢂt Heidelberg
Im Neuenheimer Feld 270, 69120 Heidelberg, FRG
Fax : (+49)6221-54-8401
E-mail: uwe.bunz@oci.uni-heidelberg.de
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.201303277.
Scheme 2. Coupling of diaminoarene 10 to dibromide 11; screening for
optimum reaction conditions.
Chem. Eur. J. 2013, 19, 15089 – 15092
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15089

shows slightly lower yields for the coupling reaction, but is
more suitable for use in microwave vessels. 6) In some
cases, under more forcing reaction conditions, both expected
product 12 and oxidation product 13 form in the coupling
reaction. A more detailed description of the reaction screen-
ing is given in the Supporting Information. The highest yield
for 12 (53%) was obtained after 16 h in the microwave reac-
tor, with 1a as the catalyst and Cs2CO3 as the base, at
1208C. The oxidation of 12 into 13 in the presence of MnO2
occurs in high yields.
Figure 2 displays the crystal packing of azacene 13, a pack-
ing that is different from that of its isostructural hydrocar-
bon, which packs in a pairwise herringbone fashion.[8–10] In
contrast, 13 arranges with an isolated one-dimensional stack
of the aromatic cores. This pattern is a compromise between
the pairwise herringbone arrangement of the hydrocarbon
isostere, 5,14-bis(TIPS-ethynyl)pentacene (TIPS=trisopro-
Scheme 3. Synthesis of N,N’-dihydrodiazapentacene 15 (in parentheses:
corrected yields, based on recovered starting material).
A
diazahexacene
(19,
Scheme 4) was obtained from
the coupling reaction between
diaminoarene 6 and dibromide
11. Unfortunately, the mild
base Cs2CO3 did not work as
well as it had with previous ex-
amples and the yield of isolated
coupling product 17 was only
29%, with 18a,b also being iso-
lated in 16% yield. Harsher re-
action conditions, that is, con-
ducting the reaction at 1508C
and using the stronger base
NaOtBu
surprisingly
gave
Figure 2. Crystal structure and one-dimensional stacked packing of diazapentacene 13. Hydrogen atoms have
been omitted for clarity.
better results (49% of 17) and
also suppressed the formation
of 18. Oxidation of 17 using
pylsilyl), and the brick-wall motif of more electron-poor aza-
pentacenes. The competing steric and electronic effect is
confirmed by the strong bend of the TIPS-ethynyl substitu-
ents, indicating a high crystal-packing pressure.
MnO2 gave diazahexacene 19 in 81% yield after chromatog-
1
raphy. The H NMR and 13C NMR spectra and high-resolu-
tion mass spectrum support the formation of 19.
Following the successful synthesis of compounds 12 and
13, we were interested to obtain improved results for N,N’-
dihydroazapentacene 15, which had previously been ob-
tained in poor yields (18%) by the coupling of diaminoar-
ene 6 to ortho-benzoquinone, followed by oxidation with
MnO2.[7] The reaction conditions as described above for the
synthesis of 12 were used and provided 12% of 15 and 8%
of oxidation compound 9 (Scheme 3a). We assume that the
low yields are due to catalyst poisoning upon reduction of
Pd2+. Better results were achieved when the coupling of 6
to dibromide 14 was performed in the presence of benzoqui-
none with 1a as the catalyst and Cs2CO3 as the base at
1208C (Scheme 3b). Surprisingly, the benzoquinone does
not oxidize 15 into 9, however, it seems to re-oxidize a re-
duced intermediate of the catalyst thereby leading to an im-
proved yield of 15 (53%).
Scheme 4. Synthesis of N,N’-dihydrodiazahexacene 17 followed by oxida-
tion.
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Chem. Eur. J. 2013, 19, 15089 – 15092

Pd-Catalyzed Coupling of Non-Activated Dibromoarenes to 2,3-Diaminoarenes
COMMUNICATION
The isolation of X-ray quality crystals of 19 that were
grown by slow solvent evaporation from a solution of the
compound in a mixture of hexane and dichloromethane
(Figure 3; for CIF data see the Supporting Information) was
surprising because the Diels–Alder dimerization product 20
had formed over time by reaction of one diazahexacene
core with the TIPS-ethynyl group of a second molecule, the
end product of the reaction. The dimerization product, 24,
had formed instead in 76% yield (X-ray crystal structure,
Figure 4). The bond lengths and bond angles of 24 are in ex-
À
cellent agreement with the expected values. The two C C
bonds that connect the aromatic system upon formation of
a tricyclododecane cage display the expected bond-length
increase to 1.61 ꢄ; the dimerization product 24 is analogous
to some of the dimerization
products recently observed.[10]
The heptacene 23 was probably
formed but is not persistent.
Perhaps a silyl group carrying
larger substituents (tBu3Si- or
(Me3Si)3Si-) might stabilize the
diazaheptacenes, in
a similar
fashion to the situation de-
scribed for large acenes.[10]
We have developed an effi-
cient coupling procedure that
allows the synthesis of N,N’-di-
hydrodiazapentacenes, -hexa-
cenes, and -heptacenes using
non-activated ortho-dibromoar-
enes. Pd-catalyzed coupling of
aromatic diamines with non-ac-
tivated aromatic dibromides is
Figure 3. Dimerization product 20 from azahexacene 19. Ellipsoids are shown at 50% probability levels and
hydrogen atoms have been omitted for clarity.
core of which stays intact. The dimerization of diazahexa-
cene 19 is in contrast to the behavior of the tetraazahexa-
cenes, which do not undergo Diels–Alder dimerization.
This synthetic strategy should also allow the construction
of diazaheptacenes; the coupling of 6 to dibromide 21 fur-
nished dihydrodiazaheptacene 22 in a satisfactory 74% yield
(toluene, 1508C, microwave; Scheme 5). These larger sys-
tems form in higher yield with fewer side products, even
though harsher reaction conditions are employed. Attempts
to oxidize dihydrodiazaheptacene 22 into 23 using MnO2 led
to a red fluorescent solution, indicating that 23 was not the
Figure 4. Single-crystal X-ray structure of the dimer 24 from azahepta-
cene 23. Ellipsoids are shown at 50% probability levels and hydrogen
atoms have been omitted for clarity.
most successful when catalyst 1a is employed. The coupling
reaction described works better for larger N,N’-dihydrodia-
zacenes than it does for smaller azaacenes, even though
harsher reaction conditions are needed. Cyclic voltammetry
shows that the larger NH compounds are more difficult to
oxidize and therefore cannot reduce the Pd2+ species, which
is necessary for the coupling (see the Supporting Informa-
tion). A practical solution to the unwanted reduction of Pd
in the formation of the smaller azaacenes was found through
addition of benzoquinone to the reaction mixture, an addi-
tive that seems to keep Pd in the correct oxidation state.
Scheme 5. Synthesis of diazaheptacene 23 and its dimer 24 by Pd-cata-
lyzed amination.
Chem. Eur. J. 2013, 19, 15089 – 15092
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15091

U. H. F. Bunz et al.
Overall, this concept provides access to heteroacenes of
greater structural diversity, some derivatives being virtually
inaccessible previously. The potential of azaacenes as active
species in thin-film transistors is now clear, but the material
basis and the synthetic access to structures of this type has
been limited and, up to now, has mainly been based on clas-
sical condensation reactions. The coupling method described
herein could open the way to unknown azaacene topologies.
The application of the presented method to prepare novel,
stable derivatives of the higher oligoazaacenes is currently
ongoing.
Acknowledgements
This work was supported by a grant from the “Deutsche Forschungsge-
meinschaft (DFG)” (Bu771/7–1). JUE thanks the “Deutsche Telekom-
Stiftung” for a scholarship.
Keywords: alkynes
·
azapentacenes
·
heteroacenes
·
palladium catalysis
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Experimental Section
General procedure for palladium-catalyzed amination in dioxane: In an
oven-dried microwave vial under an atmosphere of argon, a mixture of
the ortho-diamine (1.0 equiv), the ortho-dihalide (1.5 equiv), and the pre-
catalyst 1a (5 mol%) were dissolved in dry dioxane. Degassing the re-
sulting mixture for 10 min by bubbling argon through the mixture was
followed by the addition of Cs2CO3 (4.0 equiv). The microwave vial was
sealed and the reaction mixture was stirred for 16 h at 1208C in the mi-
crowave reactor. Subsequently it was diluted with a saturated, aqueous
solution of ammonium chloride (2 mL). The phases were separated and
the aqueous phase was extracted with diethyl ether (2ꢅ10 mL). The com-
bined organic layers were washed with brine and dried over sodium sul-
fate. Flash column chromatography gave the clean N,N’-dihydroazaacene.
Synthesis of 12: The general procedure was applied to 10 (50 mg,
96.4 mmol) and 11 (41.0 mg, 0.143 mmol, 1.5 equiv) using precatalyst 1a
(3.90 mg, 4.82 mmol, 5 mol%) and Cs2CO3 (125 mg, 0.384 mmol, 4 equiv)
in dioxane (2 mL). Flash column chromatography (silica gel, petroleum
ether/ethyl acetate) yielded 12 (53%, 33.1 mg, 51.5 mmol) as a green-
yellow solid. Rf =0.68 (petroleum ether/ethyl acetate=9:1); m.p. 1158C;
1H NMR (300.19 MHz, CDCl3, 258C): d=1.22–1.28 (m, 42H), 6.54 (s,
2H), 6.77 (s, 2H), 7.12–7.18 (m, 2H), 7.21–7.26 (m, 2H), 7.37–7.44 (m,
2H), 7.78–7.85 ppm (m, 2H); 13C {1H} NMR (75.48 MHz, CDCl3, 258C):
d=11.54, 19.06, 99.05, 100.62, 103.86, 107.47, 124.48, 124.67, 125.10,
125.94, 129.35, 130.46, 131.02, 134.43, 139.99 ppm; IR: n˜ =3398, 3057,
2939, 2890, 2862, 2125, 1469 cmÀ1
; UV/Vis (hexane): lmax (e)=472,
472 nm (20975 molÀ1 dm3 cmÀ1); fluorescence (hexane): lmax =476 nm;
HRMS (EI): m/z calcd for C42H54N2Si2: 642.3820 [M]+; found: 642.3849;
m/z calcd for C39H47N2Si2: 599.3272 [MÀC3H7]+; found: 599.3260.
Oxidation of 12: N,N’-dihydroazaacene 12 was dissolved in dichlorome-
thane (1 mL per 20 mg) and an excess of MnO2 (800 wt% of the N,N’-di-
hydroazaacene) was added. After 1 h, the reaction mixture was filtered
and the filtrate was evaporated. Flash column chromatography (silica gel,
petroleum ether/ethyl acetate) yielded 13 (92%, 117 mg, 183 mmol) as
a dark green solid that forms crystals with a metallic appearance. Rf =
0.63 (petroleum ether/ethyl acetate=9:1); m.p. 2388C; 1H NMR
(300.08 MHz, CDCl3, 258C): d=1.33–1.43 (m, 42H), 7.41–7.48 (m, 2H),
7.56–7.63 (m, 2H), 8.04–8.12 (m, 2H), 8.68–8.75 (m, 2H), 8.88 ppm (s,
1H); 13C {1H} NMR (75.48 MHz, CDCl3, 258C): d=11.82, 19.15, 103.35,
108.83, 121.05, 127.03, 127.93, 128.18, 128.40, 128.96, 135.48, 135.94,
141.29, 142.14 ppm; IR: n˜ =3052, 2939, 2890, 2862, 2149, 2124, 1461,
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Received: August 20, 2013
Published online: October 7, 2013
1387 cmÀ1
;
UV/Vis
(hexane):
lmax
(e)=661,
661 nm
(21085 molÀ1 dm3 cmÀ1); HRMS (EI): m/z calcd for C42H52N2Si2: 640.3669
[M]+; found: 640.3633; m/z calcd for C39H45N2Si2: 597.3116 [MÀC3H7]+;
found: 597.3126; elemental analysis calcd (%) for C42H52N2Si2: C 78.69,
H 8.18, N 4.37; found: C 78.63, H 8.10, N 4.25.
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Chem. Eur. J. 2013, 19, 15089 – 15092