Synthesis of 2,2′-biquinolines from o-isocyanostyrenes

Article abstract of DOI:10.3987/COM-00-9095

The heating of o-isocyanostyrenes (1) in diglyme at reflux temperature for 2 h afforded the corresponding 2,2′-biquinolines (2) via a coupling/electrocyclic reaction in fair-to-good yields.

Full text of DOI:10.3987/COM-00-9095

HETEROCYCLES, Vol. 55, No. 1, 2001, pp. 33 - 36, Received, 27th October, 2000
SYNTHESIS OF 2,2'-BIQUINOLINES FROM
o-ISOCYANOSTYRENES
Kazuhiro Kobayashi,*Junpei Yonemori, Akihiro Matsunaga, Taichi Kitamura,
Miyuki Tanmatsu, Osamu Morikawa, and Hisatoshi Konishi
Department of Materials Science, Faculty of Engineering, Tottori University,
Koyama-minami, Tottori 680-8552, Japan
Abstract- The heating of o-isocyanostyrenes (1) in diglyme at reflux temperature
for 2 h afforded the corresponding 2,2’-biquinolines (2 ) v i a a
coupling/electrocyclic reaction in fair-to-good yields.
Extensive studies on the synthesis utilizing metal complexes having a 2,2’-biquinoline ligand as a catalyst
have recently been reported.1 A number of elegant methods have been reported to prepare this class of
compounds.2 However, little is known about the simple general synthesis of substituted 2,2’-biquinolines.
Recent work in our laboratory demonstrated that o-isocyanostyrenes were oxidized with mCPBA to o-
isocyanatostyrenes, which underwent electrocyclic reaction to give quinolin-2(1H)-ones in good yields.3
We have found that 4,4’-disubstituted 2,2’-biquinolines (2) can be obtained simply by heating o-
isocyanostyrenes (1) in diglyme at reflux temperature.
The starting isocyanides (1) were prepared as follows. Treatment of o-aminostyrenes, which were
commercially available or readily prepared using the procedure by Smith and Livinghouse4 or Bell et al.,5
with formic acid in refluxing toluene gave the corresponding formamide, which were then dehydrated with
phosphorous oxychloride in the presence of triethylamine in THF to give 1 in high overall yields. While
these isocyanides appeared to be somewhat unstable, most of them could be purified by column
chromatography on silica gel and storable for prolonged periods at refrigerator temperature.
The transformation of 1 into 2,2’-biquinolines (2) was carried out as outlined in Scheme 1. The results are
given in the Table, which indicates that the yields of the products are fair-to-good. The progress of the
reactions could be readily monitored by IR spectral measurement. The characteristic absorption band of
isocyanide group (ν ca. 2120 cm–1) disappeared during about 2 h heating. The reactions also proceeded
smoothly in other solvents, such as p-cymene, mesitylene, or xylene, but did not proceed to any
appreciable extent in refluxing toluene. For example, the reaction of 1d in refluxing toluene gave only 30 %

1
R
N
1
R
2
R
2
R
diglyme
reflux
N
R
NC
2
R
1
1
2
Scheme 1.
Table. Preparation of 4,4’-disubstituted 2,2’-biquinolines 2
Product 2 (Yield/%)a
Entry
Starting isocyanide 1
1a (R1 = Ph, R2 = H)
1
2
3
4
5
2a (66)
1b (R1 = o-Tol, R2 = H)
1c (R1 = 4-MeOC6H4, R2 = H)
1d (R1 = Me, R2 = H)
1e (R1 = Ph, R2 = Cl)
2b (68)
2c (52)
2d (75)
2e (62)
a Yields are based on 1 and isolated products after recrystallization.
1
R
2
1
1
R
R
R
2
2
R
R
2
1
N
C
N
R
N C C N
2
3
R
4
1
1
1
R
R
2
2
R
R
[O]
N
N
R
2
N
N
2
R
1
1
R
5
6
Scheme 2.
yield of the desired product (2d) after 12 h heating.
The following procedure is typical for the preparation of 4,4’-disubstituted 2,2’-biquinolines (2). A solution
of 1-isocyano-2-(1-phenylethenyl)benzene (1a) (0.39 g, 1.9 mmol) in diglyme (19 mL) was heated at

reflux temperature for 2 h, when the IR spectral analysis of the mixture did not reveal presence of any
isocyano compounds. The resulting mixture was allowed to cool to room temperature to give yellow
precipitate, which was collected by filtration. The solid was recrystallized from chloroform to give pure 2a
(0.26 g, 66%): mp 371 ˚C (lit.,6 362 ˚C).7
Although we have no evidence for the intermediaries of the present reaction, a possible pathway leading to
the formation of biquinolines (2) from isocyanides (1) may be illustrated in Scheme 2. Coupling of two
isocyanides on their isocyano carbon gives the dimeric intermediate (3).8 This then undergoes
electrocyclization9 to give the keteneimine intermediate (4). Isomerization of 4 to form a quinoline ring,
giving the intermediate (5), is followed by the second electrocyclic reaction to yield the dihydrobiquinoline
derivative (6), which is oxidized with oxygen probably contaminated in the reaction mixture to lead to the
biquinoline product (2).
As a limitation of the present reaction, it should be noted that similar heating of 1-isocyano-2-[(E)-2-phenyl-
1-methylethenyl]benzene gave an intractable mixture of products, from which only a trace amount of the
expected biquinoline derivative was detected. This result indicates that 3,3’-disubstituted 2,2’-biquinolines
cannot be obtained under the present conditions. This may be due to the strained hindrance of the transition
state of electrocyclic intermediate such as 3 and/or 5.
In summary, we have shown that the reaction described here offers a convenient method for the preparation
of 4,4’-disubstituted 2,2’-biquinolines. The method is not only of simple manipulations, but also efficient
because of the ready availability of the starting materials. A study on the synthesis of heterocycle-fused 2,
2’-bipyridine derivatives is currently under way in our laboratory.
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1
7.
2b: mp 322 ˚C (CHCl3); IR (KBr disk) 1604, 1588, 758 cm–1; H NMR (270 MHz, CDCl3) δ
2.12 (6H, s), 7.3–7.55 (12H, m), 7.71 (2H, ddd, J = 8.2, 6.6, 1.6 Hz), 8.22 (2H, d, J = 8.2 Hz),
8.81 (2H, s); MS m/z 436 (M+, 64), 435 (100). Anal. Calcd for C32H24N2: C, 88.04; H, 5.54; N,
6.42. Found: C, 87.94; H, 5.42; N, 6.21. 2c: mp 324–325 ˚C (CHCl3); IR (KBr disk) 1608, 1590,
1248 cm–1; 1H NMR (270 MHz, CDCl3) δ 3.94 (6H, s), 7.11 (4H, d, J = 8.6 Hz),7.52 (2H, t, J =
8.2 Hz), 7.60 (4H, d, J = 8.6 Hz), 7.74 (2H, t, J = 8.2 Hz), 8.01 (2H, d, J = 8.2 Hz), 8.26 (2H, d,
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1
385–386 ˚C (CHCl3); IR (KBr disk) 1604, 1588, 699 cm–1; H NMR (270 MHz, CDCl3) δ
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C, 75.49; H, 3.83; N, 5.85.
8.
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