Synthesis of 6,6'-diamino-2,2'-biquinoline and 2,2'-bi-1,6- naphthyridine

Article abstract of DOI:10.1055/s-1999-6064

High-yield synthesis and characterization of the new heterocycles 6,6'- diamino-2,2'-biquinoline (3), 6,6'-bis(N,N-dimethyl-amino)-2,2'-biquinoline (4), and 2,2'-bi-1,6-naphthyridine (5) are described. The preparation of 3 and 4 is based on the coupling of 2-amino-6-chloroquinoline and 2-chloro-6- dimethylaminoquinoline in the presence of NiCl₂·6H₂O/PPh₃/Zn in DMF (NiCRA). Compound 5 was synthesized through a condensation reaction of 4- aminopyridine-3-carbaldehyde and butane-2,3-dione.

Full text of DOI:10.1055/s-1999-6064

PAPER
959
Synthesis of 6,6’-Diamino-2,2’-biquinoline and 2,2’-Bi-1,6-naphthyridine
Christoph Janiak,* Stephan Deblon, Lars Uehlin
Department of Chemistry, Universität Freiburg, Albertstr. 21, D-79104 Freiburg, Germany
Fax +49(761)2036147; E-mail: janiak@uni-freiburg.de
Received 16 November 1998; revised 28 December 1998
Abstract: High-yield synthesis and characterization of the new het-
X
X
erocycles 6,6'-diamino-2,2'-biquinoline (3), 6,6'-bis(N,N-dimethyl-
amino)-2,2'-biquinoline (4), and 2,2'-bi-1,6-naphthyridine (5) are
described. The preparation of 3 and 4 is based on the coupling of 2-
amino-6-chloroquinoline and 2-chloro-6-dimethylaminoquinoline
in the presence of NiCl2◊6H2O/PPh3/Zn in DMF (NiCRA). Com-
pound 5 was synthesized through a condensation reaction of 4-ami-
nopyridine-3-carbaldehyde and butane-2,3-dione.
N
N
6a -X = -NH2
6b -X = -CN
6c -X = -NCS
The idea behind the use of such functionalized bridging/
chelating 2,2’-bipyridine-type ligands is to have cross-
connecting blocks (tectons) for coordination polymers
based on the endo-chelation of two ligands with an appro-
priate metal center as depicted in 7 or to supply functional
donor atoms within the inner walls of a porous coordina-
tion polymer or other metallacyclic polyhedra8 (Figure).
Key words: spacer ligands, coupling reactions, NiCRA, biquino-
line, binaphthyridine
Chelating and bridging nitrogen ligands, such as 2,2’-bi-
pyridine (1) or 4,4’-bipyridine (2) are of constant interest
in transition metal coordination chemistry. Long spacer
ligands are currently investigated as building blocks for
supramolecular complexes and for the construction of
(porous) metal frameworks.1–3 The generation of such
frameworks is a promising path in the search for stable
microporous metal-organic networks that exhibit revers-
ible guest exchange and possibly selective catalytic activ-
ity.1,4
N
N
N
N
M
N
N
N
7
N
N
N
N
1
2
M
M
M
= spacer ligand with
additional functionality
R2N
N
N
NR2
N
N
N
N
M
3 R = H
4 R = Me
5
Figure. Schematic illustration of molecular boxes or coordination po-
lymers built from spacer ligands such as 5 with additional functiona-
lities
Multidentate ligands which combine chelating and bridg-
ing coordinative properties have so far been little investi-
gated in the construction of metal coordination polymers.
We report here on the synthesis of the long spacer and
chelating ligands 6,6’-diamino- and 6,6’-bis(N,N’-dimeth-
ylamino)-2,2’-biquinoline (3 and 4) and 2,2’-bi-1,6-naph-
thyridine (5). This is a continuation of our recent
investigations on the coordination behavior of modified
2,2’-bipyridine ligands such as ambidentate 5,5’-diamino-
2,2’-bipyridine (6a),5 5,5’-dicyano-2,2’-bipyridine (6b)6 or
the 5,5’-diisothiocyanato-2,2’-bipyridine ligand (6c) as
well as on modified and ambidentate tris(pyrazolyl)borate
ligands.7
The biquinolines 3 and 4 are obtained through a Semmel-
hack coupling9 of the 2-chloroquinolines 8 and 9 in 2–2.5
hours in yields of 82 and 86%, respectively (Scheme 1). A
nickel-containing complex reducing agent (NiCRA) con-
sisting of NiCl2◊6H2O/PPh3/Zn/DMF, i.e. with zinc as the
reducing agent,10 was best employed as a stoichiometric
coupling reagent.11
The starting materials for the coupling reaction, the 6-
amino- and 2-chloro-6-dimethylaminoquinoline (8 and
9), in turn, were prepared according to Effenberger and
Hartmann12 starting from aniline or 4-(dimethylami-
no)aniline, respectively, and 3-ethoxypropenoyl chloride
Synthesis 1999, No. 6, 959–964 ISSN 0039-7881 © Thieme Stuttgart · New York

960
C. Janiak et al.
PAPER
relative reaction rate is considerably slower for the cleav-
age of a CF3 group by a factor of 1010 versus a CCl3
group,17 the trifluoro derivative could still be cleaved
within a few hours in good yield.18 Aminolysis of the tri-
fluoromethyl ketone 13 with p-(dimethylamino)aniline, to
give 11 directly, was tried but found unsuccessful.
Scheme 1
O
(10) (Scheme 2). In the first step, 3-ethoxypropenoic
amide (11) is obtained, which is then cyclized with miner-
al acids to the 2-hydroxyquinolines 12 in good yield.
While the cyclization of the unsubstituted amide occurred
at room temperature with concentrated HCl and was com-
plete within 15 minutes, cyclization of the dimethylami-
noanilide 11 required the use of warm concentrated
H2SO4 and a reaction time of 24 hours. The decreased re-
activity can be traced to the negative inductive effect of
the protonated amino function which makes the electro-
philic substitution on the aromatic ring more difficult.
Even stronger electron-withdrawing substituents such as a
nitro group would fully suppress the cyclization under
moderate conditions. The 2-hydroxyquinoline 12 is trans-
fered with phosphoryl chloride into the corresponding 2-
haloquinoline 9.
Br
OEt
1. Zn
2. HC(OEt)3
O
(EtO)2CH
OEt
TosOH
100 oC
O
O
EtO
OEt
COCl2, 20%
in toluene
NaOH
EtO
43%
ref. 13
30% overall
H2O
X = F
93%
O
Cl
X = Cl
84%
(CF3CO)2O
or
10
CCl3COCl
pyridine
ref. 15
SOCl2
96%
OH
KOH
O
O
toluene
EtO
CX3
EtO
92%
13
ref. 18
Scheme 3
A reductive coupling of 2-chloro-1,6-naphthyridine with
a NiCRA in analogy to the above synthesis of 3 and 4
should have been a possibility, yet the sole known synthe-
sis of 2-chloro-1,6-naphthyridine is low yielding.19 Thus,
a different strategy was chosen, in which the bond con-
necting the two naphthyridines was formed during the
course of the ring closure reaction. The preparation of
substituted quinolines20 from 2-aminobenzaldehyde or of
naphthyridine derivatives21 from aminopyridinecarbalde-
hydes and methyl ketones has been investigated. Starting
from 4-aminopyridine-3-carbaldehyde (16) some 1,6-
naphthyridine derivatives have been described.22 Com-
pound 16 is obtained by acid hydrolysis of N-(3-formyl-4-
pyridyl)-2,2-dimethylpropionamide (15). The latter is, in
turn, synthesized from 4-aminopyridine, 2,2-dimethylpro-
pionoyl chloride, and dimethylformamide via 2,2’-dime-
thyl-N-(4-pyridyl)propionamide (14) as indicated in
Scheme 4. We found that the yield of 15 could be in-
creased from 60 to 80% in comparison to the previous
reports23 if the product was worked up by distillation in-
stead of recrystallization. In the case of 16, twofold subli-
mation proved advantageous in comparison to the
described recrystallization.
Scheme 2
3-Ethoxypropenoyl chloride (10) was derived both from
ethyl bromoacetate according to Shaw and Warrener13
(30% overall yield in 4 steps, Scheme 3) and from ethyl
vinyl ether by the addition of phosgene according to Paul
and Tchelicheff.14 For the latter, the use of a 20% phos-
gene solution in toluene instead of liquid phosgene, as
originally proposed, was found feasible here and 10 was
obtained in 43% yield in a one-step reaction (Scheme 3).
As an alternative to phosgene, the vinyl ether could also
be acylated with trifluoroacetic anhydride or trichloro-
acetyl chloride in very high yield in the presence of pyri-
dine.15 For the mechanism of the addition of an acyl halide
or anhydride to a vinyl ether see ref. 16. The trihalomethyl
ketones 13 were then cleaved with wet KOH in toluene to
the free acid as part of the haloform reaction. Although the
Synthesis 1999, No. 6, 959–964 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Synthesis of 6,6’-Diamino-2,2’-biquinoline and 2,2’-Bi-1,6-naphthyridine
961
NMR 7.26 ppm, 13C NMR 77.0 ppm; C6D6:1 H NMR 7.19 ppm, 13
C
O
NMR 128.0 ppm; 1,4-dioxane: 1H NMR 3.58 ppm, 13C NMR 66.5
ppm). IR-spectra were measured on a Perkin-Elmer 783 infrared
spectrophotometer as KBr disks or nujol mulls. Mass spectra were
obtained on a GC/MS Finnigan MAT in solid-probe EI mode at an
ionization energy of 70 eV. Elemental analyses were carried out
with a Perkin-Elmer Elemental Analyzer E 240 C.
NH2
1. 2 n-BuLi, THF,
-78 °C
O
NEt3
HN
+
CH2Cl2
Cl
2. DMF, 0 °C
3. 6N HCl, 0 °C
N
H
N
80%
14
O
6-Amino-2-chloroquinoline (8)
O
O
HN
1. 3N HCl
reflux
NH2
6-Amino-2-chloroquinoline (8) was prepared from aniline and 3-
ethoxypropenoyl chloride (10) according to refs.12, 24 and 25. The
hitherto unreported NMR data for 8 are given below.
H
2. K2CO3
N
N
1H NMR (CDCl3): d = 4.00 (br s, 2 H, NH2), 6.86 (d, 1 H, J = 2.7
Hz, H-5), 7.14 (dd, 1 H, J = 8.9, 2.7 Hz, H-7), 7.23 (d, 1 H, J = 8.5
Hz, H-3), 7.80 (d, 1 H, J = 8.9 Hz, H-8), 7.81 (d, 1 H, J = 8.5 Hz, H-
4).
80%
15
16
Scheme 4
13C NMR (CDCl3): d = 107.3 (C-5), 122.1, 122.3 (C-3,7), 128.3 (C-
4-Aminopyridine-3-carbaldehyde (16) is then condensed
with butane-2,3-dione under basic conditions to give 2,2’-
bi-1,6-naphthyridine (5) (Scheme 5). However, the exper-
imental conditions required considerable optimization.
When the base was added dropwise to the solution of both
starting materials at room temperature, followed by heat-
ing to reflux, the yield was only 17%. In order to decrease
the amount of homocondensation products of butane-2,3-
10), 129.5 (C-8), 136.6 (C-4), 142.6 (C-9), 145.1 (C-6), 146.6 (C-2).
6,6´-Diamino-2,2´-biquinoline (3), Typical Procedure
In a 250 mL three-necked flask were placed NiCl2◊6H2O (6.20 g, 26
mmol) and Ph3P (27.3 g, 104 mmol). The flask was evacuated and
refilled three times with argon. Anhyd DMF (200 mL) was added
under inert gas and the color of the solution turned rapidly to blue.
After Ph3P and NiCl2◊6H2O had completely dissolved, zinc powder
(1.80 g, 29 mmol) was added under inert gas at 50°C and the color
dione, the base was reduced to 0.18 equivalent. Further- of the solution turned slowly to brown-red. After stirring this mix-
ture for 1 h, a solution of 8 (4.60 g, 26 mmol) in DMF (20 mL) was
added dropwise into the mixture. Stirring was continued for 4 h at
50°C at which time the starting material could not be detected any-
more by TLC (eluent EtOAc). The mixture was then concentrated
more, a highly diluted solution of butane-2,3-dione was
added dropwise to a solution of 16 and sodium hydroxide
in ethanol. Comparative experiments also showed that ad-
dition under reflux gave a higher yield than addition at
in vacuum to half of its volume. After adding H2O (500 mL) the
room temperature followed by reflux. At last, a slight ex-
cess of diacetyl could compensate for its loss due to self-
condensation. Altogether, a maximum yield of 81% could
be reached in the condensation reaction to form 5. An
overview on the optimization experiments is given in the
Table.
mixture was carefully poured into conc ammonia (350 mL) and
stirred for 18 h. The color of the solution turned blue because of the
formation of hexaammine-nickel(II) complexes. The PPh3 precipi-
tate was removed by filtration and the filtrate was extracted with
CH2Cl2 (3 î 100 mL). The combined organic phases were treated
three times with half-concentrated HCl (100 mL each) to separate
the diaminobiquinoline from Ph3P. During this procedure strongly
colored amine hydrochlorides were formed. The combined acidic
aqueous phases were carefully neutralized with aq 10% Na2CO3 so-
lution (30 mL). The product 3 separated as a yellow powder and was
purified by recrystallization from DMSO/H2O; yield: 3.0 g (82%);
mp 309°C.
H
0.18 eq. NaOH
O
O
NH2
EtOH
2
+
78 oC, 11 h
81%
N
O
16
N
N
N
N
Table Reaction of 16 with Butane-2,3-dione (Scheme 5) Under
Different Conditions
5
Reaction Conditions
Amount of Bu-
tane-2,3-dione
(equiv)a
Yield of 5
(%)
Scheme 5
Solvents were dried according to standard procedures over potassi-
um metal (Et2O, THF), CaH2 (DMF), distilled and stored under ar-
gon. CHCl3, CH2Cl2 and toluene were purchased with a residual
water content of less than 0.05% and used as such. All aniline start-
ing materials were purified by vacuum distillation under argon prior
to use. Commercial Ph3P was dried for 24 h in vacuum at 50°C.
Technical grade POCl3 was distilled over a short Vigreux column
under inert gas (bp 106°C) and stored under argon in the dark.
NaOH added dropwise to 16
and butane-2,3-dione
1.00
17
48
Butane-2,3-dione added
dropwise to 16 and NaOH
at r.t.
1.00
Butane-2,3-dione added
dropwise to 16 and NaOH
at reflux
1.00
1.10
1.16
1.30
1.40
68
71
81
68
60
NMR spectra were recorded on a Bruker ARX200 (200.1 MHz for
1H, 50.3 MHz for 13C) or a Varian O-300 instrument (300.0 MHz
for 1H, 75.4 MHz for 13C) and calibrated against the solvent signal
1
1
(DMSO-d6: H NMR 2.53 ppm, 13C NMR 39.5 ppm; CDCl3: H
a Equivalents per stoichiometric molar amount.
Synthesis 1999, No. 6, 959–964 ISSN 0039-7881 © Thieme Stuttgart · New York

962
C. Janiak et al.
PAPER
3-Ethoxypropenoyl-4-(N,N-dimethylamino)anilide (11)
1H NMR (DMSO-d6): d = 5.70 (br s, 4 H, NH2), 6.83 (d, 2 H, J = 2.4
Hz, H-5,5’), 7.18 (dd, 2 H, J = 9.0, 2.4 Hz, H-7,7’), 7.79 (d, 2 H, J =
9.0 Hz, H-8,8’), 8.02 (d, 2 H, J = 8.7 Hz, H-3,3’), 8.46 (d, 2 H , J =
8.6, H-4,4’).
13C NMR (DMSO-d6): d = 104.8 (C-5,5’), 118.3 (C-7,7’), 121.7 (C-
3,3’), 129.7 (C-10,10’), 130.0 (C-8,8’), 133.5 (C-4,4’), 141.2 (C-
9,9’), 147.5 (C-6,6’), 150.9 (C-2,2’).
To a solution of p-(N,N-dimethylamino)aniline (4.00 g, 29.4 mmol)
in anhyd toluene (100 mL) was added anhyd Et3N (5 mL, 3.77 g,
37.3 mmol). After warming this mixture to about 100°C, a solution
of 10 (3.93 g, 29.2 mmol) in anhyd toluene (20 mL) was added
dropwise to give a yellow slurry. After complete addition, the mix-
ture was refluxed for 1 h, then the solvent was removed in vacuum.
The remaining solid was extracted with THF (100 mL) and the so-
lution filtered off from the insoluble Et3N◊HCl. Solvent removal
from the filtrate yielded a brown solid, which was recrystallized
from CHCl3 to give 11 as light-yellow crystals; yield: 4.45 g (65%);
mp 151°C.
1 H NMR (CDCl3): d = 1.26 (t, 3 H, J = 7.0 Hz, OCH2CH3), 2.87 [s,
6 H, N(CH3)2], 3.81 (q, 2 H, J = 7.0 Hz, OCH2CH3), 5.31 (d, 1 H, J
= 12.1 Hz, =CHCONH ), 6.64 (dt, 1 H, J = 6.0, 2.3 Hz, arom. m-
CH), 7.33 (br s, 2 H, arom. o-CH), 7.46 (br s, 1 H, CONH), 7.54 (d,
1 H, J = 12.1 Hz, =CHOEt).
IR (KBr): n = 3442 w, 3374 m, 3316 w, 3036 w, 1630 s, 1602 m,
1589 m, 1518 w, 1507 w , 1490 s, 1428 m, 1308 m, 1272 m, 1268
m, 1161 m, 1138 w, 1068 w, 1031 m, 962 w, 913 w, 868 w, 840 w,
728 w, 660 w, 600 w (br) , 556 w, 521 w, 422w cm–1.
MS: m/z (%) = 286 (100, M+), 143 (0.5, M/2+).
Anal. C18H14N4 (286.3): calcd. C 75.51, H 4.93, N 19.55; found C
75.30, H 5.33, N 19.37.
The numbering scheme for the NMR notation of 3 and 4 is as fol-
lows:
13C NMR (CDCl3 ): d = 14.5 (CH3), 40.9 [N(CH3)2], 66.9 (OCH2),
99.3 (=CHCO), 113.0 (arom. C-3,5), 121.7 (arom. C-2,6), 128.5
(arom. C-1), 147.8 (arom. C-4), 160.0 (NHCO), 165.1 (=CHOEt).
4
3
3' 4'
2'
2
5 10
10' 5'
IR (nujol): n = 3295 m, 3252 m, 3195 w, 3040 w, 1658 s, 1622 m,
1612 m, 1598 m, 1527 s, 1518 s, 1468 s, 1421 w, 1408 w, 1395 w,
1367 w, 1344 m, 1322 w, 1294 w, 1252 m, 1238 m, 1194 w, 1153
s, 1108 w, 1062 w, 1012 w, 962 w, 948 w, 925 w, 860 w, 842 w, 818
w, 810 w, 786 w, 758 w, 738 w, 712 w cm–1.
6
6'
R2N
N
N
9'
NR2
9
7
8
8' 7'
MS: m/z (%) = 234 (75, M+), 136 [100, (Me2N – C6H4 – NH)+H]+],
135 [40, (Me2N – C6H4 – NH)+], 121 (9, (Me2N – C6H4)+H+], 108
[7, (Me2N – C6H4 – NH) – HCN+], 99 (10, HC=CHOEt+).
6,6´-Bis-(N,N-dimethylamino)-2,2´-biquinoline (4)
The synthetic route as given above for 6,6´-diamino-2,2´-biquino-
line (3) was followed. Starting from 9 (0.80 g, 3.8 mmol), the
biquinoline was obtained as a light-yellow powder; yield: 0.56 g
(86%); mp 348°C.
Anal. C13H18N2O2 (234.3): calcd. C 66.64, H 7.74, N 11.96; found
C 66.23, H 7.96, N 11.52.
2-Hydroxy-6-(dimethylamino)quinolone (12)
1H NMR (CDCl3): d = 3.15 (s, 12 H, CH3), 6.86 (d, 2 H, J = 2.7 Hz,
H-5,5'), 7.38 (dd, 2 H, J = 9.4, 2.9 Hz, H-7,7'), 8.05 (d, 2 H, J = 9.2
Hz, H-.8,8'), 8.08 (d, 2 H, J = 8.4 Hz, H-3,3'), 8.63 (d, 2 H, J = 8.7
Hz, H-4,4').
13C NMR (CDCl3): d = 105.1 (C-5,5'), 119.2, 119.5 (C-3,3',7,7'),
129.7 (C-10,10'), 130.4 (C-8,8'), 134.6 (C-4,4'), 141.9 (C-9,9'),
148.7 (C-6,6'), 152.8 (C-2,2').
To concd H2SO4 (30 mL) cooled to –10°C was added 11 (8.00 g,
34.2 mmol) in small portions. A clear yellow solution was produced
after 5 min which was then warmed to 50°C and the reaction was
monitored by TLC [1 drop of the reaction mixture was neutralized
with aq satd NaHCO3 solution (2 mL) and brought onto the TLC-
plate with the starting material as reference; eluent: EtOAc]. The re-
action was complete after 24 h. The mixture was poured onto ice
(200 g) and the pH was carefully raised with 5 M NaOH up to 12–
13. The precipitate was separated by filtration, dissolved in CHCl3,
filtered again, the solvent removed and the product recrystallized
from acetone to give bright-yellow needle-shaped crystals; yield:
4.60 g (72%).
1H NMR (CDCl3): d = 2.97 (s, 6 H, CH3), 6.68 (d, 1 H, J = 9.4 Hz,
H-3), 6.78 (d, 1 H, J = 2.6 Hz, H 5), 7.08 (dd, 1 H, J = 9.0, 2.7 Hz,
H-7), 7.38 (d, 1 H, J = 9.0 Hz, H-8), 7.73 (d, 1 H, J = 9.5 Hz, H-4),
12.84 (br s, 1 H, OH).
13C NMR (CDCl3): d = 41.1 (CH3), 108.9 (C-5), 117.0 (C-7), 118.5
(C-3), 120.8 (C-10), 121.3 (C-8), 130.9 (C-9), 140.6 (C-4), 146.7
(C-6), 164.0 (C-2).
IR (nujol): n = 1695 w , 1594 m, 1542 m, 1495 s, 1492 s, 1382 s,
1369 m, 1358 w, 1292 w, 1280 w, 1268 w, 1220 w, 1182 w, 1175
w, 1152 w, 1130 w, 1076 w, 1061 m, 1004 w, 946 w, 880 w, 842 w,
760 w, 736 w cm–1.
+
MS: m/z (%) = 342 (100, M+), 326 (6, M – CH3 ), 171 (M/2+).
Anal. C22H22N4 (342.4): calcd. C 77.16, H 6.47, N 16.36; found C
77.01, H 6.44, N 16.25.
2-Chloro-6-(N,N-dimethylamino)quinoline (9)
3-Ethoxypropenoyl Chloride (10)
Anhyd Et3N (2.6 ml, 2.0 g, 20 mmol) was added to a 20% solution
of phosgene in toluene (100 mL, 189 mmol) at –15°C. After stirring
for 10 min, ethyl vinyl ether (18.1 mL, 13.6 g, 190 mmol) was added
dropwise, such that the temperature never exceeded 0°C. When the
addition was complete, the cooling bath was removed and stirring
was continued for 48 h at r. t. The solvent and the 2-(chloroethyl)
ethyl ether formed were distilled off. Vacuum distillation of the res-
idue then gave 10 as a pale yellow oil; yield: 10.9 g (43%); bp 55°C/
2.5 mbar (Lit.14 bp 105 °C/35 Torr).
1H NMR (CDCl3): d = 1.31 (t, 3 H, J = 7.0 Hz, CH3), 4.02 (q, 2 H,
J = 7.0 Hz, CH2O), 5.46 (d, 1 H, J = 12.1 Hz, =CHCOCl), 7.74 (d,
1 H, J = 12.1 Hz, EtOCH=).
13C NMR (CDCl3): d = 14.2 (CH3), 68.7 (CH2O), 102.7 (=CHCO),
164.5 (C=O), 168.1 (EtOCH=).
IR (nujol): n = 3400 w (br), 3140 w, 2724 w, 1658 s, 1621 s, 1565
w, 1512 w, 1468 s, 1428 m, 1418 m , 1384 w, 1368 m, 1340 w, 1284
w, 1270 w, 1242 w, 1200 w, 1162 w, 1158 w, 1118 s, 1069 w, 1030
w (br) , 972 w, 968 w, 953 w, 946 w, 925 w, 905 w, 842 s, 813 m,
753 w, 686 w cm–1.
MS: m/z (%) = 189 (100, M+), 188 (18, M – H+), 173 [15, (M –
OH)+H+], 172 (32, M – OH+), 159 (8, [M – OH – HCN+), 145 (11,
+
+
M – NMe2 ), 128 (18, M – OH – NMe2 ), 116 (11, [M – NMe2 – CO
– H+).
Anal. C11H12N2O (188.2) calcd. C 70.20, H 6.38, N 14.90; found C
70.43, H 5.78, N 15.08.
Synthesis 1999, No. 6, 959–964 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Synthesis of 6,6’-Diamino-2,2’-biquinoline and 2,2’-Bi-1,6-naphthyridine
963
Reaction of POCl3 with 12 to form 9
mmol) in absolute EtOH (50 mL) was added dropwise within 3 h.
The initially yellow solution turned brown and a colorless precipi-
tate occurred. After complete addition, the mixture was refluxed for
another 8 h. The precipitate was filtered, washed with EtOH (3×10
mL), with acetone (10 mL) and recrystallized from 1,4-dioxane
(300 mL) to give the product as a faint brown solid; yield: 2.10 g
(81%); mp. >300°C.
1H NMR (dioxane-d8): d = 7.97 (d, 2 H, J = 5.9 Hz, H-3,3'), 8.40 (d,
2 H, J = 8.8 Hz, H-8,8'), 8.76 (d, 2 H, J = 5.9 Hz, H-4,4'), 8.92 (d, 2
H, J = 8.5 Hz, H-7,7'), 9.29 (s, 2 H, H-5,5').
Compound 12 (1.0 g, 5.3 mmol) was suspended in POCl3 (15 mL)
and heated to reflux for 3 h. After removal of excess POCl3 by dis-
tillation, the semi-solid residue was poured onto ice (100 g), made
alkaline to a pH of 8–9 with aq 10% Na2CO3 solution and the pre-
cipitate filtered. After drying in vacuum, the product was purified
by sublimation at 140°C/0.2 mbar to give 9 as yellow crystals;
yield: 0.95 g (87%); mp 75°C.
1H NMR (CDCl3): d = 3.06 (br s, CH3), 7.08 (d, 1 H, J = 2.5 Hz, H-
5), 7.23 (d, 1 H, J = 9.4 Hz, H-3), 7.40 (dd, 1 H, J = 8.6, 2.5 Hz, H-
7), 7.85 (d, 1-H, J = 8.6 Hz, H-8), 7.92 (d, 1-H, J = 9.4 Hz, H-4).
13C NMR (dioxane-d8) = d = 121.4 (C-8,8'), 122.6 (C-3,3'), 124.7
(C-10,10'), 137.4 (C-4,4'), 148.3 (C-7,7'), 150.9 (C-2,2'), 153.8 (C-
5,5'), 159.9 (C-9,9').
13C NMR (CDCl3): d = 41.9 (CH3), 108.3 (C-5), 120.2 (C-7), 122.7
(C-3), 128.0 (C-10), 129.6 (C-8), 137.5 (C-4), 147.0 (C-2); no sig-
nals were found for the quartenary carbon atoms 6 and 9.
IR (KBr): n = 3045 w, 3010 w, 1618 s, 1593 m, 1550 w, 1480 w,
1450 m, 1395 m, 1375 w, 1307 w, 1255 w, 1212 w, 1168 w, 1070
w, 950 m, 855 m, 845 s, 788 w, 660 w, 640 m, 520 m cm–1.
IR (KBr): n = 2930 m, 2890 m, 2818 m, 1653 s, 1580 s, 1560 m,
1518 s, 1453 m, 1427 m, 1372 s, 1197 m, 1156 m, 1138 m, 1099 s,
1021 m, 941 s, 848 m, 816 s, 806 m, 712 m, 642 m cm–1.
MS: m/z (%) = 258 (100, M+), 129 (16, M – C8H5N2+ = M/2+), 102
Anal. C11H11ClN2 (206.7) calcd. C 64.00, H 5.33, N 13.55; found C
64.11, H 5.22, N 12.33%.
(12, M/2 – HCN+).
Anal. C16H10N4 (258.3) calcd. C 74.40, H 3.90, N 21.69; found C
74.03, H 3.78, N 21.41%.
N-(3-Formyl-4-pyridyl)-2,2-dimethylpropionamide (15)
2,2’-Dimethyl-N-(4-pyridyl)propionamide (14; 22.0 g, 123 mmol)
(prepared according to ref. 23) was dissolved in anhyd THF (400
mL) under an inert atmosphere and cooled to –78°C. Within 1 h, a
1.6 M hexane solution of BuLi (200 mL, 0.32 mol) was added drop-
wise. Then, the orange solution was warmed to 0°C, stirred for 3 h,
and anhyd DMF (27.0 g, 0.38 mol) in anhyd THF (100 mL) was
added. Subsequently, the solution was warmed to r.t. and stirred for
an additional 45 min. The mixture was poured onto a mixture of 6
N HCl (250 mL) and ice (250 g). After stirring for 5 min, the solu-
tion was neutralized with K2CO3 (190 g, 1.4 mol) and extracted with
Et2O (3 î 200 mL). The combined organic phases were dried
(Na2SO4) and the solvent removed in vacuum. The brown residue
was distilled over an angular tube in a liquid nitrogen cooled flask
(130°C bath temperature/0.1 mbar) to give a light yellow solid;
yield: 20.3 g (80%); mp 59–63°C (Lit.23 mp 60–63°C).
Acknowledgement
The work was supported by the Fonds der Chemischen Industrie
and DFG.
References
(1) Batten, S. R.; Robson, R. Angew. Chem. 1998, 110, 1559;
Angew. Chem., Int. Ed. 1998, 37, 1460.
Janiak, C. Angew. Chem. 1997, 109, 1499. Angew. Chem., Int.
Ed. Engl. 1997, 36, 1431. Yaghi, O. M.; Li, H.; Davis, C.;
Richardson, D.; Groy, T. L. Acc. Chem. Res. 1998, 31, 474.
(2) Martell, A. E.; Hancock, R. D. Metal Complexes in Aqueous
Solutions, Plenum Press: New York, 1996.
1H NMR (CDCl3): d = 1.37 (s, 9 H, CH3), 8.60 (s, 2 H, H-2,6), 8.82
von Zelewsky, A. Stereochemistry of Coordination
Compounds, Wiley: Chichester, 1996.
Lehn, J. M. Supramolecular Chemistry, VCH: Weinheim,
1995.
(s, 1 H, H-5), 10.01 (s, 1 H, CHO), 11.23 (br s, 1 H, NH).
13C NMR (CDCl3): d = 28.9 (CH3), 40.6 (CMe3), 113.8 (C-5), 117.7
(C-3), 147.1 (C-4), 166.1 (C-6), 167.7 (C-2), 179.5 (NC=O), 194.4
(CHO).
Constable, E. C. Prog. Inorg. Chem. 1994, 42, 67.
(3) For recent work with 4,4'-bipyridine, see for example:
Tong, M.-L.; Ye, B.-H.; Cai, J.-W.; Chen, X.-M.; Ng, S. W.
Inorg. Chem. 1998, 37, 2645.
4-Aminopyridine-3-carbaldehyde (16)
Compound 15 (20.0 g, 97 mmol) was dissolved in 3 N HCl (200
mL) and heated to reflux for 8 h. During this time, the initially yel-
low solution turned brown. The mixture was extracted with Et2O (3
î 200 mL each). The aqueous phase was made alkalic with K2CO3
(95 g, 0.7 mol) and extracted with CHCl3 (3 î 200 mL). The com-
bined organic phases were dried (Na2SO4) and the solvent was re-
moved in vacuum. The yellow-brown residue was sublimed twice
(115°C bath temperature/0.1 mbar) and eventually recrystallized
from methylcyclohexane to give a colorless solid; yield: 9.5 g
(80%); mp 115–116°C (Lit.23 mp 114–116°C).
1H NMR (CDCl3): d = 6.47 (d, 1 H, J = 5.8 Hz, H-5), 6.53 (br s, 2
H, NH2), 8.15 (d, 1 H, J = 5.8 Hz, H-6), 8.50 (s, 1 H, H-2), 9.86 (s,
1 H, CHO).
13C NMR (CDCl3): d = 110.4 (C-5), 115.7 (C-3), 152.7 (C-6), 157.4
(C-2), 193.3 (CHO).
MacGillivray, L. R.; Groeneman, R. H.; Atwood, J. L. J. Am.
Chem. Soc. 1998, 120, 2676.
Blake, A. J.; Hill, S. J.; Hubberstey, P.; Li, W.-S. J. Chem.
Soc. Dalton Trans. 1998, 909.
Tong, M.-L.; Chen, X.-M.; Yu, X.-L.; Mak, T. C. W. J. Chem.
Soc. Dalton Trans. 1998, 5.
Power, K. N.; Hennigar, T. L.; Zaworotko, M. J. New. J.
Chem. 1998, 177.
Stang, P.; Olenyuk, B. Acc. Chem. Res. 1997, 30, 502.
Yaghi, O. M.; Li, H.; Groy, T. L. Inorg. Chem. 1997, 36, 4292.
Lu, J.; Paliwala, T.; Lim, S. C.; Yu, C.; Niu, T.; Jacobson, A.
J. Inorg. Chem. 1997, 36, 923.
Carlucci, L.; Ciani, G.; Proserpio, D. M.; Sironi, A. J. Chem.
Soc. Dalton Trans. 1997, 1801.
Lossier, P.; Zaworotko, M. J. Angew. Chem. 1996, 108, 2957;
Angew. Chem,. Int. Ed.Engl. 1996, 35, 2779.
Yaghi, O. M.; Li, H. J. Am. Chem. Soc. 1996, 118, 295.
Hunter, C. A. Angew. Chem. 1995, 107, 1181; Angew. Chem.,
Int. Ed. Engl. 1995, 34, 1079.
2,2’-Bi-1,6-naphthyridine (5)
4-Aminopyridine-3-carbaldehyde (16; 2.44 g, 20 mmol) was dis-
solved in absolute EtOH (40 mL) and combined with an aqueous so-
lution of NaOH (70.0 mg, 1.75 mmol, 2 mL). The mixture was
heated to reflux and a solution of butane-2,3-dione (1.00 g, 11.6
(4) Brunet, P.; Simard, M.; Wuest, J. D. J. Am. Chem. Soc. 1997,
119, 2737.
Synthesis 1999, No. 6, 959–964 ISSN 0039-7881 © Thieme Stuttgart · New York

964
C. Janiak et al.
PAPER
(5) Janiak, C.; Deblon, S.; Wu, H.-P.; Kolm, M. J.; Klüfers, P.;
Piotrowski, H.; Mayer, P. Eur. J. Inorg. Chem., submitted for
publication.
(6) Wu, H.-P.; Janiak, C.; Rheinwald, G.; Lang, H. J. Chem. Soc.,
Dalton Trans. 1999, 183.
(12) Effenberger, F.; Hartmann, W. Chem. Ber. 1969, 102, 3260.
Effenberger, F.; Hartmann, W. Angew. Chem. 1964, 76, 188.
(13) Shaw, G.; Warrener, R. J. Chem. Soc. 1958, 153.
(14) Paul, E.; Tchelitcheff, S. (Soc. Us. Chim. Rhone-Poul.), US
Patent 2768176, Chem. Abstr. 1957, 51, 5818.
(7) For our recent work with the ambident
(15) Tietze, L.-F., Meier, H., Voß, E. Synthesis 1988, 274.
(16) Hojo, M. Synthesis 1986, 1016.
Tietze, L.; Meier, H.; Voß, E. Synthesis 1988, 274.
(17) Guthrie, J. P.; Cossar, J. Can. J. Chem. 1990, 68, 1640.
(18) Hojo, M.; Masuda, R.; Kokuryo, Y.; Shioda, H. Chem. Lett.
1976, 499.
(19) Kobayashi, Y.; Kumadaki, I.; Sato, H. Chem. Pharm. Bull.
1969, 17, 1045.
(20) Smirnoff, A. Chem. Ber. 1921, 54, 802.
hydrotris(triazolyl)borate ligand, see for example:
Janiak, C.; Scharmann, T. G.; Green, J. C.; Parkin, R. P. G.;
Kolm, M. J.; Riedel, E.; Mickler, W.; Elguero, J.; Claramunt,
R. M.; Sanz, D. Chem. Eur. J. 1996, 2, 992.
Janiak, C.; Scharmann, T. G.; Günther, W.; Hinrichs, W.;
Lentz, D. Chem. Ber. 1996, 129, 991.
Janiak, C.; Scharmann, T. G.; Hemling, H.; Lentz, D.;
Pickardt, J. Chem. Ber. 1995, 128, 235.
(8) Stang, P. J.; Olenyuk, B. Acc. Chem. Res. 1997, 30, 502.
Wu, H.-P.; Janiak, C.; Uehlin, L.; Klüfers, P.; Mayer, P.
Chem. Commun. 1998, 2637.
(9) Semmelhack, M. F.; Helquist, P.; Jones, L. D.; Keller, L.;
Mendelson, L.; Ryono, L. S.; Gorszynski Smith, J.; Staufer, R.
D. J. Am. Chem. Soc. 1981, 103, 6460.
(21) Hawes, E.; Gorecki, D. J. Heterocycl. Chem. 1972, 9, 703.
(22) Hawes, E.; Gorecki, D. J. Heterocycl. Chem. 1974, 11, 151.
(23) Piao, M.; Imafuku, K. J. Heterocycl. Chem. 1996, 33, 389.
Turner, J. J. Org. Chem. 1983, 48, 3401.
(24) Bennett, G.; Crofts, C.; Hey, D. J. Chem. Soc. 1949, 227.
(25) Capps, J.; Hamilton, C. J. Am. Chem. Soc. 1938, 60, 2104.
(10) Tiecco, M.; Testaferri, L.; Tingoli, M.; Chianelli, D.;
Montanucci, M. Synthesis 1984, 736.
Chan, K. S.; Tse, A. K.-S. Synth. Commun. 1993, 23, 1929.
(11) Colon, I.; Kelsey, D. J. Org. Chem. 1986, 51, 2627.
Colon, I.; Kwiatkowski, G. T.; Mareska, L. M. Eur. Pat. Appl.
12201, 1980; Chem. Abstr. 1980, 94, P65293.
Article Identifier:
1437-210X,E;1999,0,06,0959,0964,ftx,en;H10598SS.pdf
Synthesis 1999, No. 6, 959–964 ISSN 0039-7881 © Thieme Stuttgart · New York