Synthesis and further rearrangements of 7-(2-cycloalken-1-yl)-8-quinolinols

Article abstract of DOI:10.1007/s00706-014-1167-z

Rearrangement reaction of 8-(cycloalkenyloxy)quinolines and the acid-catalyzed cyclization of the products were investigated. These reactions afforded insights on interesting new heterocyclic systems. Depending on the size of the cycloalkenyl moiety, we c

Full text of DOI:10.1007/s00706-014-1167-z

Monatsh Chem (2014) 145:993–999
DOI 10.1007/s00706-014-1167-z
ORIGINAL PAPER
Synthesis and further rearrangements of 7-(2-cycloalken-1-yl)-8-
quinolinols
•
Mercedesz Torincsi Pal Kolonits Lajos Novak
•
¨
Received: 11 November 2013 / Accepted: 24 January 2014 / Published online: 8 April 2014
Ó Springer-Verlag Wien 2014
Abstract Rearrangement reaction of 8-(cycloalkenyl-
oxy)quinolines and the acid-catalyzed cyclization of the
products were investigated. These reactions afforded insights
on interesting new heterocyclic systems. Depending on the
size of the cycloalkenyl moiety, we could isolate benzofuro
[3,2-h]quinoline, methanooxecino[3,2-h]quinoline, metha-
nooxonino[3,2-h]quinoline, and/or spiro[cycloalkano-1,20-
furo[3,2-h]quinoline. The mechanism of the novel rear-
rangement reactions is also discussed.
Recently we have developed efficient methods for the
preparation of heteroaromatic compounds by Claisen
rearrangement and subsequent cyclization [14–17]. With
the aim of continuing efforts to synthesize novel hetero-
cyclic compounds, we have examined the preparation of
8-(cycloalkyloxy)quinolines, their sigmatropic rearrange-
ment reactions, and subsequent acid catalyzed cyclizations.
We report here the results and the preparation of new tet-
racyclic compounds.
Keywords Claisen rearrangement ꢀ Cyclization ꢀ
Furo-quinoline ꢀ Oxecino-quinoline ꢀ Oxonino-quinoline ꢀ
Ring constriction
Results and discussion
8-(Cycloalkyloxy)quinolines 3 (Scheme 1) were prepared
from 8-hydroxyquinoline (1). Treatment of 1 with sodium
hydride afforded the corresponding anion, which was then
reacted with 3-bromocycloalk-1-enes 2. These reactions
gave 8-(cycloalkyloxy)quinolines 3 in good to excellent
yields. The products were then subjected to thermal-
assisted and/or microwave-assisted electrocyclic reaction.
The thermal reactions were performed in chlorobenzene at
reflux, and the Claisen rearrangement needed 80 h to give
compounds 4 in acceptable yield. We obtained essentially
the same yield when we kept ethers 3 at 130 °C for 8 h
under microwave irradiation.
Introduction
8-Hydroxyquinoline, a chelating agent, was a very versatile
reagent in various organic reactions [1–8]. It was used as a
stabilizer of hydrogen peroxide in rocket fuel oxidizers.
The copper-8-quinolate, as well as the heterocyclic com-
pound itself, exhibits antiseptic, growth inhibition, and
pesticidal properties [9, 10]. The 8-alkoxyquinolinium
salts, especially the lower ethers, also have significant
antibacterial activities [11]. 8-Tosylaminoquinoline sup-
presses macrophage-mediated inflammation by inhibition
of the production of NO and PGE [12, 13].
The acid-catalyzed intramolecular cyclization of com-
pounds 4 was performed with sulfuric acid at 100 °C. Starting
with 4a, the cyclization reaction afforded, besides the
expected benzofuro[3,2-h]quinoline 5a, the isomeric metha-
nooxocino[3,2-h]quinoline 6a, in a ratio of 1:2; i.e., the 6-exo-
trig-like process was favorable [18–20]. The cyclization
reactionwas significantly faster when we used the more acidic
trifluoromethanesulfonic acid (pKa = -15). The reaction
took place at r.t. and yielded predominantly compound 6a
(38 %), besides a small amount of compound 5a (6 %).
¨
M. Torincsi ꢀ P. Kolonits ꢀ L. Novak (&)
Department of Organic Chemistry and Technology, Budapest
University of Technology and Economics, Research Group
for Alkaloid Chemistry, Hungarian Academy of Sciences,
´
Gellert ter 4, Budapest 1111, Hungary
e-mail: l-novak@mail.bme.hu
´
123

¨
M. Torincsi et al.
994
Scheme 1
n
[3,3]
NaH
+
N
N
O
OH
Br
3
2
1
n
H
n
H
N
H2SO4
or F3CSO3H
N
N
OH
+
O
O
4
H
n
H
n
1
2
3
6
2-4
a
b
c
n
n
5
n
1
a
a
1
3
b
b
2
N
H
N
O
O
8
7
n
n
a
1
b
2
The structure and stereochemistry of the new compounds
5a and 6a were established by spectroscopic methods. For
instance, an HPLC–MS experiment of compound 6a showed
a molecular ion peak at m/z = 225, indicating a molecular
formula C15H15NO. All proton and carbon signals of this
compound were assigned after extensive NMR measure-
ments using COSY, HMQC, and HMBC techniques. 1H and
13C NMR, especially NOE studies, verified the structure and
the cis-fused arrangement. Namely, the proton spectrum
showed the presence of four methylene groups; among them,
the one showing up at d = 1.98 and 2.06 ppm correlated
with the methylene at C-13. Furthermore, the two broad
singlet peaks (3.15 and 4.99 ppm), one of them originating
from an oxymethine proton, could be attributed to the pro-
tons at the annelation (C-2 and C-6). The cis-annelation was
confirmed by NOE correlation. The important NOE inter-
actions of compound 6a are shown in Fig. 1.
Acid-catalyzed intramolecular cyclization of com-
pound 4c afforded a mixture of three compounds in a ratio
of 5:5:1 (yield 56 %). Here, besides the expected metha-
nooxecino [3,2-h]quinoline 6b and the spiro compound
7b, we also isolated a methyl-substituted compound 8.
1
The structure of the latter was established by H and 13C
NMR spectra, and NOE investigation. The 1H NMR
spectrum of compound 8 was similar to that of 6b
except the presence of a signal of a methyl group
(d = 1.70 ppm). The carbon signal (d = 31.96 ppm) also
suggested the presence of a methyl group in the molecule.
The significant NOE correlation between the methyl
protons and the protons at C-14, and the lack of same with
the annellation proton at C-7 (3.21 ppm), suggested the
cis-fused structure (Fig. 1).
A plausible mechanism for the formation of compound 8
is proposed in Scheme 3. On the protonated starting com-
pound 9c, the [1,2]-alkyl migration took place, which
relieved the strain of the cyclooctenyl moiety of the mol-
ecule. Deprotonation of the intermediate 12 yielded
compound 13, on which acid-catalyzed intramolecular
cyclization afforded compound 8 (the same type of ring
constriction reaction was observed earlier during the bro-
mination of trans-cyclooctene [21, 22]).
In the analogue cyclization reaction of the homolog 4b we
obtained furo[3,2-h]quinoline 5b and a spiro analog 7a
approximately in equal amounts, in both sulfuric acid-cata-
lyzed and trifluoromethanesulfonic acid-catalyzed processes
(yields 39 and 46 %, respectively). The formation of the
spiro compound could be the result of a consecutive [1,2]-
alkyl migration, [1,2]-H shift, and cyclization (Scheme 2).
123

Synthesis and rearrangements of 7-(2-cycloalken-1-yl)-8-quinolinols
995
9.8%
1.98
3.7%
12.1%
2.21
H ax
2.21
H
1.85
ax
H
3.12
eq
13
1.87
3.21
2.06
3.8% Heq
H
H
H 2.21
H
H
1.64
ax
14
H
H
H
H
6
1.95
7
1.83
3.5%
Heq
3.5%
2
2
1.70
CH3
Heq
4.97
eq
2.31
H
H
H
2.00
1.48
O
H
O
Heq
H
2.6%
7.40
Hax
1.37
N
N
6a
8
Fig. 1 Selected NOE correlations of compounds 6a and 8
spectrophotometer. H NMR and 13C NMR spectra were
obtained on a Bruker DRX-500 spectrometer operating at
500 and 125 MHz, respectively. All NMR spectra are
reported in ppm relative to TMS. MS spectra were con-
ducted on Agilent 6140 quadrupole LC/MS instrument
(ESI was ?2 kV). Microwave irradiation was carried out
using a CEM Explorer microwave reactor equipped with an
automatic temperature controller and auto sampler (CEM
Corporation, Matthews, NC). Liquid chromatography was
conducted on the Agilent LCQ101 LC/MS (column:
Gemini 3 l C18, 50 9 3 mm; solvent H2O) instrument.
Merck precoated silica gel 60 F254 plates were used for
TLC, and Kieselgel 60 for column chromatography.
Quinolin-8-ol (1) was obtained from a commercial
source and was of the highest grade available. 3-Bromo-
cyclohex-1-ene (2a) [23], 3-bromocyclohept-1-ene (2b)
[24], and 3-bromocyclooct-1-ene (2c) [25] were prepared
using their literature procedures.
1
Scheme 2
In summary, novel heterocyclic compounds have been
prepared from 8-(cycloalkenyloxy)quinolines by thermal
rearrangement followed by acid-catalyzed cyclization. The
present synthetic schemes would enable access to a variety
of furoquinolines, oxocinoquinolines, oxecinoquinolines,
and spiro analogues, which would have interesting bio-
logical properties.
General procedure for preparation
of 8-(cycloalk-2-enyloxy)quinolines 3
To a cold-stirred suspension of NaH (12 mmol, 80 % in
mineral oil) in 10 cm3 DME, a solution of 1.0 g quinolin-8-
ol (1, 6.88 mmol) in 30 cm3 DME was added dropwise,
and the resulting mixture was stirred at 0 °C for 2 h. To
this mixture the appropriate bromine 2 (10 mmol) was
added dropwise, and stirring was continued at r.t. for 24 h.
The reaction mixture was quenched with 100 cm3 brine
and extracted with EtOAc (4 9 50 cm3). The combined
Experimental
Solvents were used as received from commercial suppliers,
and no further attempts were made to purify or dry them.
Melting points were determined on a Bu¨chi apparatus.
Infrared (IR) spectra were recorded on a Bruker Alpha FT
123

¨
M. Torincsi et al.
996
Scheme 3
8-((Z)-Cyclohept-2-enyloxy)quinoline (3b, C16H17NO)
Yellow oil; yield 46 %; TLC: Rf = 0.3 (hexane–ace-
organic layers were washed with 1 N NaOH solution and
water, and then dried over MgSO4. Evaporation of the
solvent under reduced pressure provided a residue which
was purified by column chromatography on silica gel using
hexane–EtOAc 6:1 as the eluent.
ꢀ
tone = 5:2); IR (KBr): m = 1,625, 1,570, 1,510, 1,480,
1,450, 1,380, 1,320, 1,260, 1,100 cm-1; 1H NMR (CDCl3):
0
0
d = 1.42 (m, 1H, C5 –H), 1.73 (m, 1H, C6 –H), 1.80 (m,
0
0
1H, C5 –H), 2.04 (m, 1H, C7 –H), 2.10 (m, 1H, C6 –H), 2.19
0
8-(2-Cyclohexen-1-yloxy)quinoline (3a, C15H15NO)
Yellow oil; yield 56 %; TLC: Rf = 0.29 (hexane–
0
(m, 1H, C4 –H), 2.28 (m, 1H, C4 –H), 2.30 (m, 1H, C7 –H),
0
0
0
5.18 (m, 1H, C1 –H), 5.91 (m, 1H, C3 –H), 5.98 (m, 1H,
0
ꢀ
EtOAc = 4:1); IR (KBr): m = 1,650, 1,610, 1,560, 1,500,
0
C2 –H), 7.03 (d, J = 8 Hz, 1H, C7–H), 7.37 (d, J = 8 Hz,
1,470, 1,370, 1,310, 1,260, 1,100 cm-1; 1H NMR (CDCl3):
1H, C5–H), 7.42 (m, 2H, C3–H and C6–H), 8.12 (d,
0
0
d = 1.70 (m, 1H, C5 –H), 1.96 (m, 1H, C5 –H), 2.07 (m,
J = 8 Hz, 1H, C4–H), 8.97 (d, J = 3.5 Hz, 1H, C8–H)
13
0
1H, C4 –H), 2.10 (m, 2H, C6 –H), 2.15 (m, 1H, C4 –H), 5.12
0
0
ppm; C NMR (CDCl3): d = 26.47 (C-50), 27.94 (C-60),
0
0
(br s, 1H, C1 –H), 5.98 (m, 1H, C3 –H), 6.02 (d, J = 11 Hz,
28.60 (C-40), 33.22 (C-70), 78.60 (C-10), 110.46 (C-7),
119.37 (C-5), 121.48 (C-3), 126.69 (C-6), 129.68 (C-4a),
130.60 (C-30), 136.05 (C-20), 136.15 (C-4), 140.55 (C-8a),
149.20 (C-2), 153.45 (C-8) ppm; MS: m/z (%) = 239 (M?,
100), 145 (M? - C7H10, 16).
0
1H, C2 –H), 7.12 (d, J = 8 Hz, 1H, C7–H), 7.36 (d,
J = 8 Hz, 1H, C5–H), 7.38 (dd, J = 8 Hz, 4 Hz, 1H,
C3–H), 7.42 (t, J = 8 Hz, 1H, C6–H), 8.09 (d, J = 8 Hz,
1H, C4–H), 8.95 (dd, J = 4 Hz, 1 Hz, 1H, C2–H) ppm; 13
C
NMR (CDCl3): d = 19.53 (C-50), 25.08 (C-40), 28.17
(C-60), 72.31 (C-10), 110.65 (C-7), 119.48 (C-5), 121.31
(C-3), 126.32 (C-20), 126.45 (C-6), 129.65 (C-4a), 131.99
(C-30), 135.73 (C-4), 141.04 (C-8a), 149.22 (C-2), 153.69
(C-8) ppm.
8-((Z)-2-Cycloocten-2-yloxy)quinoline (3c, C17H19NO)
Yellow oil; yield 46 %; TLC: Rf = 0.45 (hexane–
ꢀ
acetone = 5:1); IR (KBr): m = 1,613, 1,595, 1,497,
1,468, 1,424, 1,374, 1,314, 1,258, 1,180 cm-1; H NMR
1
123

Synthesis and rearrangements of 7-(2-cycloalken-1-yl)-8-quinolinols
997
0
0
(CDCl3): d = 1.49 (m, 1H, C5 –H), 1.57 (m, 1H, C6 –H),
1H, C3–H), 7.55 (d, J = 8.5 Hz, 1H, C6–H), 8.28 (d,
J = 8 Hz, 1H, C4–H), 8.78 (d, J = 4 Hz, 1H, C2–H), 9.8
(br s, 1H, OH) ppm; 13C NMR (CDCl3): d = 27.18 (C-50),
28.92 (C-40), 30.38 (C-60), 34.73 (C-70), 40.14 (C-10),
117.82 (C-5), 120.58 (C-3), 127.29 (C-4a), 128.83 (C-6),
132.27 (C-7), 132.30 (C-30), 135.96 (C-20), 136.00 (C-8a),
138.46 (C-4), 146.11 (C-2), 147.15 (C-8) ppm.
0
1.66 (m, 1H, C7 –H), 1.71 (m, 1H, C7 –H), 1.74 (m, 1H,
0
0
0
0
C6 –H), 1.78 (m, 1H, C5 –H), 2.03 (m, 1H, C8 –H), 2.24 (m,
0
1H, C4 –H), 2.34 (m, 1H, C8 –H), 2.37 (m, 1H, C4 –H), 5.35
0
0
0
0
0
(m, 1H, C1 –H), 5.70 (m, 1H, C2 –H), 5.80 (m, 1H, C3 –H),
7.05 (d, J = 8 Hz, 1H, C7–H), 7.35 (d, J = 8 Hz, 1H,
C5–H), 7.41 (m, 1H, C6–H), 7.43 (m, 1H, C3–H), 8.13 (d,
J = 8 Hz, 1H, C4–H), 8.98 (d, J = 4 Hz, 1H, C2–H) ppm;
13C NMR (CDCl3): d = 23.49 (C-70), 26.27 (C-60), 26.81
(C-40), 29.12 (C-50), 35.82 (C-80), 76.36 (C-10), 110.50
(C-7), 119.25 (C-5), 121.38 (C-3), 126.82 (C-6), 129.54
(C-4a), 130.17 (C-30), 132.95 (C-20), 136.34 (C-4), 140.15
(C-8a), 149.03 (C-2), 153.88 (C-8) ppm.
7-((Z)-2-Cycloocten-1-yl)-8-quinolinol (4c, C17H19NO)
Greenish crystals; yield: method A 49 %, method B 51 %;
m.p.: 107–109 °C; TLC: Rf = 0.2 (hexane–EtOAc = 4:1);
ꢀ
IR (KBr): m = 3,340, 1,505, 1,465, 1,452, 1,405, 1,380,
1,348, 1,300, 1,280, 1,180, 1,040 cm-1; 1H NMR (CDCl3):
0
0
d = 1.44 (m, 1H, C5 –H), 1.63 (m, 1H, C6 –H), 1.71 (m,
0
2H, C7 –H), 1.80 (m, 2H, C5 –H and C6 –H), 1.83 (m, 2H,
0
0
General procedures for rearrangement of ethers 3
0
0
0
C8 –H), 2.18 (m, 1H, C4 –H), 2.54 (m, 1H, C4 –H), 4.45 (m,
0
0
0
1H, C1 –H), 5.76 (m, 2H, C2 –H and C3 H), 7.34 (d,
J = 8.5 Hz, 1H, C5–H), 7.39 (dd, J = 8 Hz, 4 Hz, 1H, C3–
H), 7.54 (d, J = 8.5 Hz, 1H, C6–H), 8.15 (d, J = 8 Hz,
1H, C4–H), 8.74 (d, J = 4 Hz, 1H, C2–H), 8.8 (br s, 1H,
OH) ppm; 13C NMR (CDCl3): d = 26.26 (C-70), 26.47 (C-
40), 26.66 (C-60), 29.68 (C-50), 35.99 (C-10), 36.69 (C-80),
117.63 (C-5), 120.87 (C-3), 126.86 (C-4a), 127.65 (C-6),
128.63 (C-7), 129.68 (C-30), 132.73 (C-20), 136.64 (C-4),
137.53 (C-8a), 147.19 (C-2), 148.24 (C-8) ppm.
Method A A solution of ether 3 (3 mmol) in 50 cm3
chlorobenzene was kept at reflux for 80 h. The solvent was
evaporated under reduced pressure, and the crude product
was purified by column chromatography on silica gel
(hexane–EtOAc = 4:1).
Method B Ether 3 (5 mmol) was kept at 130 °C for 8 h
under microwave irradiation. After cooling, the reaction
mixture was dissolved in a mixture of CH2Cl2 and acetone
(5:2) and purified by column chromatography (hexane–
EtOAc = 4:1).
General procedures for cyclization
7-(2-Cyclohexen-1-yl)-8-quinolinol (4a, C15H15NO)
Greenish crystalline solid; yield: method A 47 %, method
B 52 %; m.p.: 97–98 °C; TLC: Rf = 0.52 (hexane–
of 7-(2-cycloalken-1-yl)-8-quinolinols 4
Method A A solution of 1.0 g compound 4 in 0.6 cm3
sulfuric acid was kept at 100 °C for 1 h. After cooling, the
reaction mixture was poured into 10 cm3 water; the
resulting solution was basified with 1 N NaOH solution
and extracted with CHCl3 (3 9 15 cm3). The combined
organic layers were dried over MgSO4 and the solvent was
evaporated under reduced pressure. The residue was puri-
fied by column chromatography.
Method B A solution of 1.0 g compound 4 in 1 cm3
trifluoromethanesulfonic acid was stirred at r.t. for 1 h. The
reaction mixture was poured in 1 N NaOH solution and
extracted with CHCl3 (3 9 15 cm3). The combined
organic layers were dried over MgSO4; solvent was evap-
orated in vacuo, and the residue was purified by column
chromatography.
ꢀ
EtOAc = 4:1); IR (KBr): m = 3,320 (OH), 1,625, 1,505,
1
1,460, 1,370, 1,340, 1,280, 1,230, 1,090 cm-1; H NMR
0
0
(CDCl3): d = 1.66 (m, 1H, C6 –H), 1.72 (m, 1H, C5 –H),
0
0
1.77 (m, 1H, C5 –H), 2.13 (m, 3H, C4 –H and C6 –H), 4.12
0
0
(m, 1H, C1 –H), 5.74 (dd, J = 8 Hz, 1.5 Hz, 1H, C2 –H),
0
0
5.97 (m, 1H, C5 –H), 7.28 (d, J = 8.5 Hz, 1H, C5–H), 7.35
(dd, J = 8.2 Hz, 4 Hz, 1H, C3–H), 7.43 (d, J = 8.5 Hz, 1H,
C6–H), 8.09 (d, J = 8.2 Hz, 1H, C4–H), 8.46 (br s, 1H, OH),
8.74 (dd, J = 4 Hz, 1 Hz, 1H, C2–H) ppm; 13C NMR
(CDCl3): d = 21.43 (C-50), 25.11 (C-40), 30.30 (C-60), 34.86
(C-10), 117.09 (C-5), 120.97 (C-3), 126.86 (C-4a), 127.77
(C-7), 128.00 (C-6), 128.81 (C-30), 129.97 (C-20), 135.89 (C-
4), 138.05 (C-8a), 147.73 (C-2), 148.67 (C-8) ppm.
7-((Z)-2-Cyclohepten-1-yl)-8-quinolinol (4b, C16H17NO)
Light greenish crystals; yield: method A 52 %, method B
52 %; m.p.: 80–84 °C; TLC: Rf = 0.75 (hexane–ace-
cis-6b,7,8,9,10,10a-Hexahydro[1]benzofuro[3,2-h]-
quinoline (5a, C15H15NO) and cis-3,4,5,6-tetrahydro-
2H-2,6-methanooxocino[3,2-h]quinoline (6a, C15H15NO)
Compound 5a: yield: method A 17 %, method B 6 %; light
yellow oil; TLC: Rf = 0.33 (hexane–EtOAc 4:1); HPLC:
ꢀ
tone = 5:2); IR (KBr): m = 3,340 (OH), 1,640, 1,520,
1,475, 1,405, 1,380, 1,290, 1,240 cm-1; 1H NMR (CDCl3):
0
0
d = 1.50 (m, 1H, C5 –H), 1.76 (m, 1H, C6 –H), 1.83 (m,
0
1H, C5 –H), 1.87 (m, 2H, C7 –H), 1.98 (m, 1H, C6 –H), 2.31
0
0
ꢀ
Rt = 3.764 min; IR (KBr): m = 1,613, 1,588, 1,515, 1,450,
1,435, 1,360, 1,348, 1,312, 1,300, 1,260, 1,220, 1,176,
0
(m, 2H, C4 –H), 4.27 (br s, 1H, C1 –H), 5.78 (dd,
0
J = 11 Hz, 2.5 Hz, 1H, C2 –H), 5.93 (m, 1H, C3 –H),
7.39 (d, J = 8.5 Hz, 1H, C5–H), 7.48 (dd, J = 8 Hz, 4 Hz,
1,137 cm-1; H NMR (CDCl3): d = 1.37 (m, 1H, C8–H),
1.49 (m, 1H, C7–H), 1.57 (m, 2H, C8–H and C9–H), 1.63
1
0
0
123

¨
M. Torincsi et al.
998
(m, 1H, C9–H), 1.91 (m, 1H, C10–H), 1.96 (m, 1H, C7–H),
2.30 (m, 1H, C10–H), 3.37 (m-q, J = 7 Hz, 1H, C6b-H),
4.97 (m, 1H, C10a-H), 7.31 (dd, J = 8 Hz, 4 Hz, 1H, C3–
H), 7.34 (d, J = 8 Hz, 1H, C5–H), 7.39 (d, J = 8 Hz, 1H,
C6–H), 8.11 (d, J = 8 Hz, 1H, C4–H), 8.85 (d, J = 4 Hz,
1H, C2–H) ppm; 13C NMR (CDCl3): d = 20.21 (C-9),
21.97 (C-8), 27.27 (C-10), 28.81 (C-7), 41.48 (C-6b), 84.06
(C-10a), 119.75 (C-5), 120.71 (C-3), 122.63 (C-6), 128.76
(C-4a), 131.63 (C-6a), 136.07 (C-4), 136.27 (C-11b),
149.64 (C-2), 154.75 (C-11a) ppm; MS: m/z (%) = 225
(M?, 100).
(KBr): mꢀ = 1,600, 1,566, 1,508, 1,460, 1,436, 1,361, 1,281,
1,253, 1,214, 1,184, 1,170, 1,078, 1,052, 1,037, 990 cm-1
;
1H NMR (CDCl3): d = 1.51 (m, 4H, C3–H, C4–H, and C5–
H), 1.83 (m, 2H, C2–H and C6–H), 1.95 (m, 2H, C3–H and
0
C5–H), 2.02 (m, 2H, C2–H and C6–H), 3.22 (m, 2H, C3 –
0
H), 7.32 (d, J = 8 Hz, 1H, C5 –H), 7.38 (dd, J = 8 Hz,
0
0
4 Hz, 1H, C7 –H), 7.40 (d, J = 8 Hz, 1H, C4 –H), 8.18 (d,
0
0
J = 8 Hz, 1H, C6 –H), 8.91 (d, J = 4 Hz, 1H, C8 –H) ppm;
13C NMR (CDCl3): d = 23.12 (C-3 and C-5), 25.14 (C-4),
37.32 (C-2 and C-6), 41.53 (C-30), 91.11 (C-1), 119.01 (C-
50), 120.56 (C-70), 124.57 (C-40), 125.21 (C-3a), 128.88 (C-
5a0), 134.43 (C-9a0), 137.36 (C-60), 148.67 (C-80), 153.51
(C-9b0) ppm; MS: m/z (%) = 239 (M?, 100).
Compound 6a: yield: method A 35 %, method B 38 %;
light yellow oil; TLC: Rf = 0.28 (hexane–acetone 5:2);
ꢀ
HPLC: Rt = 3.47 min; IR (KBr): m = 1,578, 1,560, 1,500,
1,455, 1,430, 1,380, 1,356, 1,345, 1,326, 1,307, 1,246,
3,4,5,6,7,8-Hexahydro-2H-2,8-methanooxecino[3,2-h]-
quinolone (6b, C17H19NO), 30H-spiro[cycloheptane-1,20-
furo[3,2-h]quinolone (7b, C17H19NO), and 2-methyl-
2,3,4,5,6,7-hexahydro-2,7-methanooxonino[3,2-h]-
quinolone (8, C17H19NO)
1,210, 1,195, 1,170, 1,111, 1,080, 1,072 cm-1; H NMR
1
(CDCl3): d = 1.37 (m, 1H, C4–H), 1.48 (m, 1H, C4–H),
1.64 (m, 1H, C3–H), 1.83 (m, 1H, C5–H), 1.85 (m, 1H, C5–
H), 1.98 (m, 1H, C13–H), 2.06 (m, 1H, C13–H), 2.31 (m,
1H, C3–H), 3.12 (br s, 1H, C6–H), 4.97 (br s, 1H, C2–H),
7.17 (d, J = 8.2 Hz, 1H, C7–H), 7.24 (d, J = 8.2 Hz, 1H,
C8–H), 7.33 (dd, J = 8.2 Hz, 4.2 Hz, 1H, C10–H), 8.05
(dd, J = 8 Hz, 1.2 Hz, 1H, C9–H), 8.90 (dd, J = 4 Hz,
1.2 Hz, 1H, C11–H) ppm; 13C NMR (CDCl3): d = 17.55
(C-4), 29.60 (C-13), 32.27 (C-6), 32.90 (C-5), 33.55 (C-3),
72.35 (C-2), 118.19 (C-8), 121.14 (C-10), 124.44 (C-6a),
128.15 (C-7), 128.53 (C-8a), 136.19 (C-9), 139.41 (C-12a),
149.43 (C-11), 151.79 (C-12b) ppm; MS: m/z (%) = 225
(M?, 100).
Compound 6b: yield: method B 25 %; light yellow oil;
HPLC:
TLC:
Rf = 0.35
(hexane–acetone
5:2);
ꢀ
Rt = 3.824 min; IR (KBr): m = 1,502, 1,451, 1,413,
1,373, 1,259, 1,214, 1,086, 1,017 cm-1; 1H NMR (CDCl3):
d = 1.30 (m, 2H, C4–H and C6–H), 1.58 (m, 1H, C5–H),
1.64 (m, 2H, C3–H and C7–H), 1.79 (m, 3H, C4–H, C5–H,
and C6–H), 2.13 (m, 1H, C15–H), 2.35 (m, 1H, C3–H), 2.42
(m, 1H, C15–H), 2.45 (m, 1H, C7–H), 3.02 (m, 1H, C8–H),
4.81 (m, 1H, C2–H), 7.26 (d, J = 8.5 Hz, 1H, C9–H), 7.28
(d, J = 8.5 Hz, 1H, C10–H), 7.34 (dd, J = 8 Hz, 4 Hz, 1H,
C12–H), 8.06 (d, J = 8 Hz, 1H, C11–H), 8.90 (d, J = 4 Hz,
1H, C13–H) ppm; 13C NMR (CDCl3): d = 22.46 (C-6),
23.72 (C-5), 24.59 (C-15), 30.39 (C-8), 30.62 (C-4), 30.86
(C-3), 36.18 (C-7), 74.19 (C-2), 118.08 (C-10), 120.78 (C-
12), 125.75 (C-8a), 127.97 (C-9), 128.00 (C-10a), 135.72
(C-11), 140.57 (C-14a), 147.52 (C-14b), 149.07 (C-13)
ppm; MS: m/z (%) = 253 (100).
cis-7,8,9,10,11,11a-Hexahydro-6bH-cyclohepta-
[4,5]furo[3,2-h]quinolone (5b, C16H17NO)
and 30H-spiro[cyclohexane-1,20-furo[3,2-h]quinolone
(7a, C16H17NO)
Compound 5b: yield: method A 19 %, method B 22 %;
light yellow oil; TLC: Rf = 0.2 (hexane–acetone 4:1); IR
ꢀ
(KBr): m = 1,622, 1,511, 1,461, 1,440, 1,423, 1,394, 1,368,
Compound 7b: yield: method A 25 %; light yellow
oil; TLC: Rf = 0.52 (hexane–acetone 5:2); HPLC:
1,359, 1,307, 1,244, 1,134, 1,114, 1,077, 1,043, 907 cm-1
;
1H NMR (CDCl3): d = 1.45 (m, 3H, C8–H, C9–H, and
C10–H), 1.72 (m, 2H, C8–H and C9–H), 1.86 (m, 2H, C7–H
and C10–H), 1.94 (m, 1H, C7–H), 2.10 (m, 1H, C11–H),
2.27 (m, 1H, C11–H), 3.78 (m, t-d, J = 9.9 Hz, 3.5 Hz, 1H,
C6b-H), 5.25 (m, t-d, J = 10 Hz, 4 Hz, 1H, C11a-H), 7.32
(br s, 2H, C5–H and C6–H), 7.34 (m, 1H, C3–H), 8.11 (d,
J = 8.5 Hz, 1H, C4–H), 8.85 (d, J = 4 Hz, 1H, C2–H)
ppm; 13C NMR (CDCl3): d = 24.19 (C-10), 28.62 (C-8),
31.22 (C-9), 31.64 (C-7), 31.81 (C-11), 47.50 (C-6b), 88.50
(C-11a), 119.35 (C-5), 120.79 (C-3), 123.22 (C-6), 128.89
(C-4a), 129.32 (C-6a), 135.46 (C-12b), 136.18 (C-4),
149.40 (C-2), 154.09 (C-12a) ppm; MS: m/z (%) = 239
(M?, 100).
Rt = 4.174 min; IR (KBr): m = 1,511, 1,462, 1,360,
ꢀ
1
1,311, 1,278, 1,259, 1,159, 1,080, 1,015 cm-1; H NMR
(CDCl3): d = 1.52 (m, 2H, C3–H and C6–H), 1.63 (m, 2H,
C4–H and C5–H), 1.72 (m, 2H, C4–H and C5–H), 1.86 (m,
2H, C3–H and C6–H), 1.98 (m-dd, 2H, C2–H and C7–H),
0
2.26 (m-dd, 2H, C2–H and C7–H), 3.25 (s, 2H, C3 –H), 7.29
0
(d, J = 8.2 Hz, 1H, C5 –H), 7.32 (dd, J = 8.2 Hz, 4.4 Hz,
0
1H, C4 –H), 7.35 (d, J = 8.2 Hz, 1H, C7 –H), 8.09 (dd,
0
0
J = 8.5 Hz, 1.5 Hz, 1H, C6 –H), 8.86 (dd, J = 4.0 Hz,
1.5 Hz, 1H, C8 –H) ppm; 13C NMR (CDCl3): d = 22.21
0
(C-3 and C-6), 29.18 (C-4 and C-5), 40.73 (C-2 and C-7),
43.29 (C-30), 94.36 (C-1), 118.93 (C-50), 120.63 (C-40),
124.00 (C-70), 124.12 (C-3a0), 128.82 (C-5a0), 136.01
(C-60), 136.05 (C-9a0), 149.51 (C-80), 154.12 (C-9b0) ppm;
MS: m/z (%) = 253 (100).
Compound 7a: yield: method A 20 %, method B 24 %;
light yellow oil; TLC: Rf = 0.5 (hexane–EtOAc 4:1); IR
123

Synthesis and rearrangements of 7-(2-cycloalken-1-yl)-8-quinolinols
999
8. Chen Y, Wang H, Wan L, Bian Y, Yang J (2011) J Org Chem
76:3774
Compound 8: yield: method B 6 %; light yellow oil;
5:2);
TLC:
Rf = 0.29
(hexane–acetone
ꢀ
HPLC:
9. Richardson WH, Hodge RL, Glover DW, Pompeo MP, Hayden
CG (2005) Composition for wood treatment comprising an
injectable aqueous wood preservative slurry having sparingly-
soluble biocidal particles and pigments. PCT Int Appl WO
2005115704 A2, Dec 8, 2005. Chem Abstr 144:24100
10. Richardson WH, Hodge RL, Glover DW, Pompeo MP, Hayden
CG (2005) Composition, method of making, and treatment of
wood with an injectable wood preservative slurry having biocidal
particles. PCT Int Appl WO 2005110692 A2, Nov 24, 2005.
Chem Abstr 143:479586
Rt = 3.802 min; IR (KBr): m = 1,512, 1,462, 1,423,
1,394, 1,368, 1,359, 1,308, 1,289, 1,244, 1,134, 1,114,
1
1,077, 1,043 cm-1; H NMR (CDCl3): d = 1.35 (m, 2H,
C4–H and C5–H), 1.50 (m, 1H, C5–H), 1.68 (m, 1H, C4–H),
1.70 (s, 3H, CH3), 1.87 (m, 1H, C6–H), 1.95 (m, 1H, C3–
H), 2.00 (m, 1H, C3–H), 2.21 (m, 3H, C6–H and C14–H),
3.21 (m, 1H, C7–H), 7.35 (d, J = 8.5 Hz, 1H, C9–H), 7.40
(d, J = 8.5 Hz, 1H, C8–H), 7.45 (dd, J = 8 Hz, 3 Hz, 1H,
C11–H), 8.20 (d, J = 8.5 Hz, 1H, C10–H), 9.03 (d,
J = 3 Hz, 1H, C12–H) ppm; 13C NMR (CDCl3):
d = 24.04 (C-5), 26.97 (C-4), 31.96 (CH3), 33.16 (C-7),
35.30 (C-6), 37.01 (C-14), 42.94 (C-3), 78.72 (C-2), 118.20
(C-9), 120.73 (C-11), 125.59 (C-7a), 128.18 (C-9a), 128.47
(C-8), 137.61 (C-10), 138.00 (C-13a), 148.09 (C-12),
149.02 (C-13b) ppm; MS: m/z (%) = 253 (100).
11. Foye OW, Marshall RJ (1964) J Pharm Sci 53:1338
12. Byeon JY, Yoo DS, Yu T, Yang Y, Kim JH, Kim E, Jeong D,
Rhee MH, Choung ES, Hong S, Cho JY (2012) Acta Pharm Sin
33:1037
13. Jung Y (2013) Pharmazie 68:146
¨
14. Torincsi M, Kolonits P, Palosi E, Novak L (2007) Synthesis 284
¨
15. Torincsi M, Kolonits P, Palosi E, Fekete J, Novak L (2008)
Arkivoc 43
¨
16. Torincsi M, Kolonits P, Fekete J, Novak L (2012) Synth Commun
42:3187
17. Kupai K, Banoczi G, Hornyanszky G, Kolonits P, Novak L
(2012) Monatsh Chem 143:1663
18. Baldwin JE (1976) J Chem Soc Chem Commun 734
19. Baldwin JE, Thomas RC, Kruse L, Silberman L (1977) J Org
Chem 42:3846
References
1. Philips JP (1956) Chem Rev 56:271
2. Arias A, Fortuno J, Counselo M, Martin A, Mastrorilli P, Todisco
S, Latronico M, Gallo V (2013) Inorg Chem 52:5493
3. Panda BK (2012) J Inorg Chem 2:49
4. Khale AA (2013) J Poly Res 20:1
5. Sosic I, Markovic B, Arenz K, Stefane B, Kos J, Gobec S (2013)
J Med Chem 56:521
20. Baldwin JE, Lusch MJ (1982) Tetrahedron 38:2939
21. Haufe G (1979) Monatsh Chem 110:121
22. Allinger NL, Tushaus LA (1967) Tetrahedron 23:2051
23. Cox RA, Swallow AJ (1958) J Chem Soc 3727
24. Dondas HA, Grigg R, Thibault S (2001) Tetrahedron 57:7035
25. Bond CW, Cresswell AJ, Davies SG, Fletcher AM, Kurasawa W,
Lee JA, Roberts PM, Russell AJ, Smith AD, Thomson JE (2009)
J Org Chem 74:6735
6. Zhang L, Wen G, Xiu Q, Guo L, Deng J, Zhong C (2012) J Coord
Chem 65:1632
7. Alam MM, Shaharyar M, Hamid H, Nazreen S, Haider A, Alam
MS (2011) Med Chem 7:663
123