Investigations on 2,3′-biquinoline series. 19. Regioselectivity of the reaction of 1,1′-dialkyl-3,3′-di(2-quinolyl)-1,1′,4, 4′-tetrahydro-4,4′-biquinolines with organomagnesium and organolithium compounds

Article abstract of DOI:10.1007/s10593-006-0071-9

1,1′-Dialkyl-3,3′-di(2-quinolyl)-1,1′,4, 4′-tetrahydro-4,4′-biquinolines react with organolithium and organo-magnesium compounds to form 1′-alkyl-2′-R-1′,2′- dihydro-2,3′-biquinolines. 2006 Springer Science+Business Media, Inc.

Full text of DOI:10.1007/s10593-006-0071-9

Chemistry of Heterocyclic Compounds, Vol. 42, No. 2, 2006
INVESTIGATIONS ON 2,3'-BIQUINOLINE SERIES.
1
9*. REGIOSELECTIVITY OF THE REACTION
OF 1,1'-DIALKYL-3,3'-DI(2-QUINOLYL)-1,1',4,4'-TETRAHYDRO-
,4'-BIQUINOLINES WITH ORGANOMAGNESIUM
AND ORGANOLITHIUM COMPOUNDS
4
1
1
2
O. A. Antonova , V. I. Goncharov , and A. V. Aksenov
1
,1'-Dialkyl-3,3'-di(2-quinolyl)-1,1',4,4'-tetrahydro-4,4'-biquinolines react with organolithium and
organo-magnesium compounds to form 1'-alkyl-2'-R-1',2'-dihydro-2,3'-biquinolines.
Keywords: 1,1'-dialkyl-3,3'-di(2-quinolyl)-1,1',4,4'-tetrahydro-4,4'-biquinolines, 1',2'-dihydro-2,3'-
biquinolines, organolithium compounds, nucleophilic substitution, Grignard reagents.
We have developed a new method for the synthesis of 1,1'-dialkyl-3,3'-di(2-quinolyl)-1,1',4,4'-
tetrahydro-4,4'-biquinolines 1 [2], which has allowed us to study their properties. In this paper we report their
reactions with organometallic compounds.
We have shown that the reaction of a diastereomeric mixture of compound 1 with organolithium
compounds in THF at room temperature gave the 1',2'-dihydro-2,3'-biquinolines 2 in close to quantitative yield.
R
N
1
R Li
N
N
N
THF
R'
N
R
N
R
1
a,b
2a–d
1
1
1
1
1
a R = Me, b R = Et; 2 a R = R = Me, b R = Me, R = Ph, c R = Et, R = Me, d R = Et, R = Ph
It is likely that the reaction occurs as shown in the scheme below. In the first stage the organolithium
behaves as a nucleophilic reagent towards compound 1. As a result of nucleophilic substitution with allylic
rearrangement compound 2 and the anion 3 are formed. It is probable that the anion loses an electron to form the
radical 4. Recombination of the latter leads to the tetraquinoline starting material 1.
_
*
_
______
For part 18 see [1].
_________________________________________________________________________________________
1
Stavropol State Medical Academy, Stavropol 355000, Russia. e-mail: sgma@statel.stavropol.ru.
2
Stavropol State University, Stavropol 355009, Russia. e-mail: nauka@stavsu.ru. Translated from Khimiya
Geterotsiklicheskikh Soedinenii, No. 2, 224-226, February, 2006. Original article submitted November 15, 2004.
0
009-3122/06/4202-0197©2006 Springer Science+Business Media, Inc. 197

R
N
N
N
N
R
+
R1 Li
1
THF
+
N
N
R1
N
R
N
R
2
3
2
1
N
N
R
4
The reaction of compound 1 with Grignard reagents occurs analogously. The yield of compound 2 in this
case is also close to quantitative.
RMgHal
1
a
2a,b
THF
EXPERIMENTAL
1
3
H NMR spectra of CDCl solutions with TMS as internal standard were recorded on a Bruker WP-200
(
200 MHz) machine. Tetrahydrofuran was dried by distillation from LiAlH . Course of reactions and purity of
4
synthesized compounds were monitored on Silufol UV-254 strips, 1:1 ethyl acetate-hexane as solvent. Flash
chromatography was carried out by a know method [3] (column: d = 60 mm, l = 50 mm) with benzene as solvent
of low polarity and ethyl acetate as the polar solvent.
Synthesis of 1'-R-2'-R-1',2'-Dihydro-2,3'-biquinolines (2) (General Method). A solution of the
corresponding organolithium compound or Grignard reagent (8 mmol) was added cautiously to a solution of a
1
,1'-dialkyl-3,3'-di(2-quinolyl)-1,1',4,4'-tetrahydro-4,4'-biquinoline 1 (1.25 mmol) in THF (10 ml). The reaction
mixture was stirred under argon at room temperature of 1 h, poured into water, and extracted with benzene
3 × 20 ml), and the solvent evaporated. The residue was purified by flash chromatography, collecting the first
colored fraction.
(
1
',2'-Dimethyl-1',2'-dihydro-2,3'-biquinoline (2a). From 1,1'-dimethyl-3,3'-di(2-quinolyl)-1,1',4,4'-
tetrahydro-4,4'-biquinoline 1a. Yield 94 (MeLi), 97% (MeMgCl); mp 168-169°C (benzene–hexane). According
to [4,5], mp 168-169°C. R 0.88 (Silufol UV-254, 1:1 ethyl acetate–hexane). A mixed melting point with a
f
1
known sample gave no depression. The H NMR spectra were identical.
1
98

1
'-Methyl-2'-phenyl-1',2'-dihydro-2,3'-biquinoline (2b). From compound 1a. Yield 98 (PhLi), 97%
(
PhMgBr); mp 138-139°C (ethanol), lit. data 138-139°C [4,5]. R 0.77 (Silufol UV-254, 1:2 ethyl acetate–
f
1
hexane). A mixed melting point with a known sample gave no depression. The H NMR spectra were identical.
'-Ethyl-2'-methyl-1',2'-dihydro-2,3'-biquinoline (2c). From 1,1'-diethyl-3,3'-di(2-quinolyl)-1,1',4,4'-
tetrahydro-4,4'-biquinoline 1b and MeLi. Yield 97%. Yellow oil. R 0.92 (Silufol UV-254, ethyl acetate–hexane
1
f
1
1
:2. H NMR spectrum, δ, ppm (J, Hz): 1.22 (3H, d, J = 6.41, 2'-CH ); 1.47 (3H, t, J = 6.95, 1'-CH CH ); 4.06
3
2
3
(
(
7
2H, m, Jgem =14.99, Jcis = 6.95, 1'-CH CH ); 5.27 (1H, q, J = 6.41, H-2'); 6.59 (1H, d, J = 8.10, H-8'); 6.70
2 3 7'8'
1H, dd, J5'6' = 7.52, J6'7' = 7.37, H-6'); 7.13 (1H, d, J5'6' = 7.61, H-5'); 7.19 (1H, dd, J6'7' = 7.37, J7'8' = 8.16, H-7');
.29 (1H, s, H-4'); 7.48 (1H, dd, J = 8.09, J = 7.14, H-6); 7.68 (1H, dd, J = 7.14, J = 8.41, H-7); 7.77 (1H,
5
6
67
67
78
d, J56 = 8.09, H-5); 7.83 (1H, d, J34 = 9.04, H-3); 8.05 (1H, J78 = 8.41, H-8); 8.09 (1H, d, J34 = 9.04, H-4).
Found, %: C 84.08; H 6.64; N 9.28. C H N O. Calculated, %: C 83.96; H 6.71; N 9.33.
2
3
22
2
1
'-Ethyl-2'-phenyl-1',2'-dihydro-2,3'-biquinoline (2d). From compound 1b. Yield 94%. Yellow oil.
1
R 0.85 (Silufol UV-254, ethyl acetate–hexane 1:2. H NMR spectrum, δ, ppm (J, Hz): 1.38 (3H, dd,
f
J
CH -CH = 7.26, JCH CH = 6.83, CH
3
); 3.75 (1H, dq, JCH -CH = 7.26, JCH -CH = 14.94, CH
a
b 3
CH CH ); 3.88 (1H, dq,
a
3
b
3
a
3
a
b
J
CH -CH = 6.83, JCH -CH = 14.94, CH CH CH ); 6.34 (1H, s, H-2'); 6.50 (1H, d, J7'8' = 8.13, H-8'); 6.70 (1H, dd,
a b 3
b
3
a
b
J5'6' = 7.53, J6'7' = 7.33, H-6'); 7.12 (1H, d, J5'6' = 7.53, H-5'); 7.15 (1H, dd, J6'7' = 7.33, J7'8' = 8.13, H-7'); 7.17
(
3H, m, H-3,4,5 Ph); 7.42 (1H, s, H-4'); 7.44 (2H, d, J = 7.14, H-2,6 Ph); 7.45 (1H, dd, J = 8.22, J = 7.04, H-
56 67
6
); 7.65 (1H, dd, J67 = 7.04, J = 8.51, H-7); 7.71 (1H, d, J = 8.22, H-5); 7.76 (1H, d, J = 8.85, H-3); 8.00
78 56 34
(
1H, d, J34 = 8.85, H-4); 8.03 (1H, d, J78 = 8.51, H-8). Found, %: C 86.32; H 6.04; N 7.64. C H N O.
23 22 2
Calculated, %: C 86.158; H 6.12; N 7.73.
This work was carried out with a financial support grant from the President of the Russian Federation for
the support of young Russian scientists and for the advancement of the scientific schools of the Russian
Federation (grant No. MD-51.2003.03).
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