Novel route to 4-(adamantan-1-yl)quinoline derivatives based on the Friedlaender condensation

Article abstract of DOI:10.1002/hlca.201100432

2,3,4-Trisubstituted quinolines, substituted with adamantan-1-yl or (adamantan-1-yl)methyl in the 4-position, were prepared from the corresponding admantan-1-yl 2-aminophenyl ketones or admantan-1-ylmethyl 2-aminophenyl ketones and ketones with an α-CH

Full text of DOI:10.1002/hlca.201100432

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Novel Route to 4-(Adamantan-1-yl)quinoline Derivatives Based on the
Friedlꢀnder Condensation
by Zuzana Kozubkova´ a), Michal Rouchala), Marek Necˇasb), and Robert Vꢀcha*a)
a
´
ˇ
) Department of Chemistry, Faculty of Technology, Tomas Bata University in Zlꢀn, Namestꢀ T.G.M. 275,
CZ-76272 Zlꢀn (phone: þ 420-576031103; fax: þ 420-576031560; e-mail: rvicha@ft.utb.cz)
b) Department of Chemistry, Faculty of Science, Masaryk University, Kamenice 5, CZ-62500 Brno
2,3,4-Trisubstituted quinolines, substituted with adamantan-1-yl or (adamantan-1-yl)methyl in the 4-
position, were prepared from the corresponding admantan-1-yl 2-aminophenyl ketones or admantan-1-
ylmethyl 2-aminophenyl ketones and ketones with an a-CH2 group. These reactions were carried out
under neat conditions or in toluene, and the products were obtained in moderate-to-excellent yields. The
scope and limitations of the examined procedures are discussed. All new compounds are fully
characterized by IR and NMR spectroscopy and mass spectrometry. The molecular structures of five new
quinolines, obtained via single-crystal X-ray diffraction analyses, are discussed.
Introduction. – The quinoline ring system is an important structural unit that occurs
in a variety of natural alkaloids, therapeutics, and synthetic analogs with interesting
biological activities. Further information on their importance can be found in recent
reviews [1]. Additionally, considerable attention has been focused in the unique
properties of the adamantane scaffold. The highly lipophilic nature of the adamantane
cage facilitates the permeability of adamantylated compounds through biological
membranes. In contrast, the formation of inclusion hostꢀguest complexes with
cyclodextrins may increase drug solubility in polar media. Combining these two areas
of chemistry, several quinoline derivatives substituted with adamantan-1-yl group have
been prepared, and their significant biological activities have been described.
In addition to more complex compounds, such as N-[4-(adamantan-1-yl)thiazol-2-
yl]-4-hydroxy-2-oxoquinoline-3-carboxamide, which possess potential antituberculosis
activity [2], N-(adamantan-1-yl)-4-oxo-1,4-dihydroquinoline-3-carboxamides, which
are CB2-selective cannabinoid receptor ligands [3], and various potential noncompe-
titive metabotropic glutamate receptor antagonists [4], some directly adamantylated
quinoline-based compounds exhibit interesting biological activities. Thus, 4-(adaman-
tan-1-yl)-2-(4-methylpiperazin-1-yl)quinoline has been studied as a 5-HT3 receptor
ligand with potential therapeutic applications against diseases related to the central
nervous system (CNS) malfunction [5]. Derivatives of 4-(adamantan-1-yl)quinoline-2-
carboxylic acid have been introduced as promising antituberculosis agents [6], and 2-
(adamantan-1-yl)quinolines have been studied for their potential antimalarial [7] or
antimicrobial [8] activities.
For the preparation of adamantylated quinoline skeletons, two approaches can be
found in the literature. While the direct substitution of the quinoline ring at C(4) under
electrochemical [9] or radical [10] conditions suffers from the formation of a complex
ꢁ 2012 Verlag Helvetica Chimica Acta AG, Zꢂrich

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mixture of products, the cyclization reaction of suitable precursors has been described
for only one compound [5]. On the other hand, 2-adamantylated quinolines and their
preparations have been reported more frequently [9][11].
In this article, we describe a new convenient synthetic route to various novel 2,3,4-
trisubstituted quinolines bearing an adamantan-1-yl moiety at C(4) via the Friedlꢀnder
condensation (for reviews, see [12]) from adamantan-1-yl 2-aminophenyl ketone/
adamantan-1-ylmethyl 2-aminophenyl ketone and the corresponding carbonyl com-
pounds.
Results and Discussion. – The key starting materials for the quinoline synthesis,
adamant-1-yl 2-nitrophenyl ketones 1a – 1c, were prepared according to a previously
published procedure. These ketones were obtained from a CuI/AlIII-catalyzed reaction
of Grignard reagents and acyl chlorides [13]. The consecutive nitration by acetyl nitrate
in Ac2O yielded a mixture of mononitrated regioisomers. The required ortho-isomers
were isolated by column chromatography in yields ranging from 35 to 80% [14a]. The
selective reduction of nitro ketones [14b] proceeded smoothly using Fe powder in
methanolic HCl, and the corresponding 2-aminophenyl ketones 2a and 2b were isolated
by column chromatography in nearly quantitative yields (Scheme 1). The rationale for
compound 2c not being obtained via this reaction is discussed below. Compounds 1a
and 1b have been prepared previously via the directed ortho-metalation of tert-butyl
phenylcarbamate, followed by the acylation with methyl adamantane-1-carboxylate [5]
and via photochemical transformation of N-phenyl-2-(adamantan-1-yl)acetamide [15].
Nevertheless, our procedure provided comparable (or, in some cases, slightly better)
yields and allowed us to circumvent the less convenient reaction conditions. The final
step to give the desired quinolines 4 was carried out in the presence of an equimolar
amount of TsOH under solvent-free conditions and with conventional heating [16].
The mixture became solid within a few minutes, probably due to the formation of the
sulfonates of the products and/or starting 2-aminophenyl ketones, and no further
reaction progress was observed. This was the most probable rationale for the decrease
in the yield of the required quinolines. In some cases, when the treatment of the mixture
during the workup procedure with base was insufficient, the corresponding quinolinium
toluenesulfonate, e.g., 4o · TsOH (Fig. 3), was isolated by crystallization. Nevertheless,
the composition of the crude product was monitored by GC/MS and/or TLC; in all
cases, no significant amount of side-products was detected, and the unreacted starting
Scheme 1

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2-aminophenyl ketones were recovered by column chromatography. Structures of the
prepared quinolines, reaction details, and yields are compiled in Table 1.
Table 1. Results of the Reactions Conducted under Neat Conditions
Entry Amine 2 Ketone 3
Product 4
Time Yield
[min] [%]
R3
R2
R1
1
2
3
4
5
6
7
8
9
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
MeC(O)CH2C(O)Me (3a)
MeC(O)CH2CO2Et (3b)
MeC(O)CO2Et (3c)
PhC(O)CH2C(O)Me (3d)
Acetophenone (3e)
4-FꢀC6H4C(O)Me (3f)
Cyclopentanone (3g)
Cyclohexanone (3h)
Cycloheptanone (3i)
Cyclooctanone (3j)
4a Ad
4b Ad
4c Ad
4d Ad
4e Ad
4f Ad
4g Ad
4h Ad
4i Ad
4j Ad
4k Ad
Ac
CO2Et Me
H
Ac
H
Me
10
15
5
10
15
95
50
33
6
44
31
63
62
52
44
19
39
CO2Et
Ph
Ph
H
4-FꢀC6H4 15
ꢀ(CH2)3ꢀ
5
15
5
5
10
5
ꢀ(CH2)4ꢀ
ꢀ(CH2)5ꢀ
ꢀ(CH2)6ꢀ
ꢀ(CH2)10ꢀ
10
11
12
Cyclododecanone (3k)
3,4-Dihydronaphthalen-1(2H)-one (3l) 4l Ad
13
14
15
2a
2b
2b
Cyclohexane-1,3-dione (3m)
Acetophenone (3e)
Cyclohexane-1,3-dione (3m)
4m Ad
4n AdCH2
4o AdCH2 ꢀC(O)(CH2)3ꢀ
ꢀC(O)(CH2)3ꢀ 15
84
22
31
H
Ph
10
5
To improve the unsatisfactory yields, the reaction was performed in a small amount
of toluene at 1008. The mixture remained liquid under such conditions, but the time
required for the reactions to go to completion was prolonged. Nevertheless, the yields
of the desired quinolines increased in all examined cases (Table 2). The significantly
lower yields (Entry 4, Table 1, and Entry 19, Table 2) may be attributed to the bulkiness
of the substituents at C(2), C(3), and C(4). In addition, the preparation of compounds
with R3 ¼ Ad, (in all cases) and R1 ¼ R2 ¼ Ph, R1 ¼ Ph and R2 ¼ Bz, R1 ¼ Ad and R2 ¼
H; or R1 ¼ Ad and R2 ¼ Me completely failed, and only the starting compounds were
recovered. The bulkiness of these substituents is the most limiting parameter in this
procedure.
Unfortunately, our attempt at extending this protocol to produce seven-membered
rings failed. Instead, the starting compound for this reaction, 1-(adamantan-1-yl)-2-(2-
nitrophenyl)ethanone (2c), underwent a cyclization during the reduction step
(Scheme 2). The expected amino ketone was not obtained, and only the corresponding

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Helvetica Chimica Acta – Vol. 95 (2012)
Table 2. Results of the Condensation Reactions Performed in Toluene
Entry
Ketone
Product
Time [h]
Yield [%]
18
19
20
21
22
23
24
3c
3d
3e
3f
3j
4c
4d
4e
4f
4j
5
12
8
6
8
68
34
96
96
95
92
96
3k
3l
4k
4l
8
8
2-(adamantan-1-yl)-2,3-dihydro-1H-indol-2-ol (5) and 2-(adamantan-1-yl)-1H-indole
(6) were detected in the mixture by GC/MS. The latter compound was the only isolated
product, and its spectroscopic data corresponded to those described in [17]. Compound
5 underwent spontaneous H2O elimination during the workup and yielded 6. The same
results were obtained, when combinations of various reducing agents (SnII, Fe0, Zn0,
Al0) with various acids (AcOH, HCl, NH4Cl) in H2O, MeOH, or EtOH were used.
Additionally, the attempt to carry out the cyclization reaction using a nitro ketone and
acetylacetone under reducing conditions [18] was unsuccessful, and again 6 was
isolated.
Scheme 2
Electrospray ionization mass spectrometry (ESI-MS) measurements of all of the
prepared compounds 4a – 4o were carried out in the positive-ion scanning mode. In the
first-order mass spectra, two peaks at m/z values corresponding to the protonated
molecular ion ([M þ H]þ) and the Na adduct of the dimer ([2M þ Na]þ), were
detected for all examined structures. With the exception of compound 4c, [M þ H]þ
represents the dominant signal in all of the first-order MS. The peak of the [M þ Na]þ
ion was observed in the positive-ion mode ESI mass spectra of some compounds.

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As an example, the results of the ESI-MS analysis of compound 4b, as well as the
suggested fragmentation pathways, are depicted in Fig. 1. The MS2 of [M þ H]þ (m/z
350) provided two signals at m/z 322 and 306, respectively. The additional
fragmentation (MS3) of these two product ions displayed similar cleavage patterns.
In comparison, the analysis of compound 4b by the electron impact ionization (EI) MS,
provided the base peak at m/z 304, and only one fragmentation pathway, beginning
with the loss of C2H5O fragment, was observed.
Fig. 1. The positive-ion mode ESI/mass spectra of compound 4b. The proposed ions corresponding to the
signals observed in the first-order mass spectra are indicated in the brackets. The fragment-ion signals in
tandem mass spectra are marked with bold arrows.
Compound 4o was crystallized from a CHCl3 solution of the crude product as the 4-
methylbenzenesulfonate salt (4o · TsOH). The torsion angle of C(8)ꢀC(7)ꢀC(14)ꢀ
C(15), describing the arrangement of the Ad substituent and the quinoline ring system,
is 85.83(16)8. This conformation is chiral, and the unit cell contains both atropisomers
arranged around the center of symmetry. The cyclohexenone ring exhibits a half-boat
conformation with the atoms C(8)ꢀC(10), C(12), and C(13) essentially in a plane (the
maximum deviation from the best plane is 0.0427(11) ꢃ for C(13)). The Cremer and
Pople puckering parameters [19] are Q ¼ 0.5023(17) ꢃ, q ¼ 130.72(19)8, and f ¼
52.9(3)8. The crystal structure is stabilized by H-bonds between the sulfonate and
the quinolinium units N(1)ꢀH(1A) ··· O(2) with a D ··· A distance of 2.7758(14) ꢃ and
a DꢀH ··· A angle of 168.58. Further stabilization via offset p ··· p stacking interactions

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is also present. The distance of C(6) from the best planes of the quinoline rings in the
positions ꢀ x þ 1, ꢀ y þ 1, ꢀ z þ 1, and ꢀ x þ 2, ꢀ y þ 1, ꢀ z þ 1 are 3.4887(16) and
1
4.0949(19) ꢃ, respectively. From the H-NMR data of 4o in CDCl3, similar chiral
conformations of the molecules may be assumed to predominate in solution. The
strongly hindered rotation of the (adamantan-1-yl)methyl substituent renders the CH2
H-atoms i.e., AdCH2, non-equivalent, and a large separation (Dd ¼ 1.33 ppm) of the
signals of the geminal AB system was observed at 308 due to the adjacent C¼O group.
The same signal separation was observed in CDCl3 at 558 (Dd ¼ 1.32 ppm) (Fig. 2).
Fig. 2. Partial 1H-NMR spectra of compound 4o in CDCl3 at 30 and at 558, respectively
The asymmetric unit of compound 4n contains two crystallographically independ-
ent molecules. The relationship between them may be expressed as conformational
enantiomers. However, the distinct conformers were observed only in the solid state.
The 1H-NMR spectrum in CDCl3 solution displaced no diastereotopic AB pattern for
CH2(16) owing to the low rotation barrier in solution at room temperature. The torsion
angles describing the mutual orientation of the benzene, quinoline, and adamantane
moieties in the first conformer, N(1)ꢀC(9)ꢀC(10)ꢀC(15) and C(8)ꢀC(7)ꢀC(16)ꢀ
C(17), are 26.8(2) and ꢀ 87.9(2)8, respectively. The values of the corresponding angles
in the second conformer are ꢀ 29.1(2) and 91.57(19)8, respectively. The crystal
structure is stabilized by weak intramolecular edge-to-face interactions. The distance of
H(14) from the best plane of the quinoline ring in the position ꢀ x þ 1, y þ 0.5, ꢀ z þ
0.5 is 2.55 ꢃ.
Compound 4g was crystallized from CHCl3 with one molecule of the solvent
included in its asymmetric unit. The cyclopentene ring adopted an envelope
conformation with the Cremer and Pople puckering parameters of Q ¼ 0.231(2) ꢃ,

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and f ¼ 288.5(6)8. The solvent molecules are stabilized in the crystal structure via weak
CꢀH ··· N interactions. The distance between H(51A) and N(1) in the ꢀ x þ 1, ꢀ y þ 1,
ꢀ z position is 2.22 ꢃ. The torsion angle C(6)ꢀC(7)ꢀC(13)ꢀC(14) describing the
orientation of the adamantane moiety and the quinoline ring is 179.49(15)8.
The quinoline ring in compound 4e, although being essentially planar, is markedly
deformed. The most affected valence angles C(5)ꢀC(6)ꢀC(7), C(5)ꢀC(6)ꢀC(1),
C(6)ꢀC(7)ꢀC(16), and C(6)ꢀC(7)ꢀC(8) are 126.15(10), 116.58(10), 123.38(9), and
116.42(10)8, respectively.
In the molecular structure of 4k, the adamantan-1-yl moiety is pushed towards the
benzene ring due to steric hindrance, whereas the deflection of the adamantan-1-yl out
of the best quinoline plane is negligible. The angle between the virtual three-fold axis,
C3 (passing through the C(20)), of the adamantan-1-yl substituent and N(1)ꢀC(11) line
is 11.75(5)8. The corresponding angles in compounds 4e and 4g are 2.83(4) and 5.58(6)8,
respectively. The angle between the best quinoline plane and the C3 axis is 86.00(3)8.
The crystal packing is stabilized only via weak Van der Waals interactions.
Asymmetric units of all of the determined structures are depicted in Fig. 3. The full
crystallographic data can be obtained free of charge via http://www.ccdc.cam.ac.uk/
data_request/cif. For the respective reference numbers, see Table 3.
Conclusions. – The described synthetic approach leading to the formation of 2,3-
disubstituted quinolines with an adamantan-1-yl or (adamantan-1-yl)methyl substitu-
ent at C(4) represents a convenient procedure to access potentially bioactive
compounds that combine properties of the quinoline ring and the adamantane moiety.
Despite the promising biological activities of some 4-(adamantan-1-yl)quinoline
derivatives [5][6], the systematic study of Friedlꢀnder condensation-based procedures
providing such compounds has not yet been published.
This work was supported by the Ministry of Education, Youth and Sports of Czech Republic (grant
No. MSM7088352101) and by the Internal Founding Agency of Tomas Bata University in Zlꢀn (project
No. IGA/6/FT/11/D and IGA/FT/2012/016).
Experimental Part
General. TLC: Alugramꢄ Sil G/UV254 foils (Machrey-Nagel); mobile phase: petroleum ether (PE)/
AcOEt 4 :1 (A) or PE/AcOEt 8 :1 (B). Column chromatography (CC): silica gel (SiO2; Merck, grade 60,
70 – 230 mesh); mobile phase the same as for TLC. M.p.: Kofler block; uncorrected. IR Spectra: Nicolet
Avatar-380 spectrophotometer; in KBr pellets; ˜n in cmꢀ1. NMR Spectra: Bruker Avance-300
spectrometer at 300.13 (1H) and 75.77 MHz (13C); d in ppm rel. to the signal of the solvent (1H:
d(residual CHCl3) ¼ 7.27 ppm; 13C: d(CDCl3) ¼ 77.23 ppm), J in Hz. EI-MS (pos.-ion): Shimadzu QP-
2010 instrument with in the range of m/z 50 – 600, using GC separation or direct inlet probe (DI) with
ion-source temp. of 2008 and ionization energy of 70 eV. Only signals exceeding rel. abundancies of 5%
are listed. GC Data were obtained using a Supelco SLB-5ms (30 m, 0.25 mm) column with He as the
carrier gas in a constant linear flow mode (38 cm · sꢀ1). The instrument was held at 1008 for 7 min, then
ramped at a rate of 258/min until the oven reached 2508, and then held for the required time. For DI, 10 ml
of a sample soln. in CH2Cl2 (30 mg · mlꢀ1) was evaporated in a DI cuvette at 508. The probe was heated at a
rate of 408/min. Elemental analyses (C, H, N): Flash EA 1112 elemental analyser (Thermo Fisher
Scientific).
ESI-MS (pos.) Measurements were performed with an amaZon X ion-trap mass spectrometer
(Bruker Daltonics, D-Bremen). Individual samples (in concentrations of 500 ng mlꢀ1) were infused into

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the ESI source in MeOH/H2O or MeCN/H2O (1:1) with a syringe pump at a constant flow rate of 5 ml
minꢀ1. Further instrument conditions: m/z range, 50 – 1000; electrospray voltage, 4.2 kV; cap. exit voltage,
140 V; drying gas temp., 3008; drying gas flow, 6.0 l · minꢀ1; nebulizer pressure, 55.16 kPa. N2 was used for
nebulizing as well as drying gas. Tandem mass spectra were obtained by collision-induced dissociation
(CID) with He as the collision gas after isolation of the required ions.
Diffraction data were collected on a KUMA KM-4 k-axis CCD diffractometer with MoKa radiation
(l ¼ 0.71073 ꢃ). The temp. during data collection was 120(2) K. The structures were solved by direct
methods and refined using full-matrix least-squares techniques using anisotropic thermal parameters for
the non-H-atoms. The software packages used were Xcalibur CCD system for the data collection/
reduction [20], ShelXTL for the structure solution and refinement [21], ORTEP-3 for drawing
preparation [22], and PLATON for the calculation of the ring puckering parameters [23].
General Procedure for the Preparation of Quinoline Derivatives 4a – 4o. Method A. 2-Aminophenyl
ketone 2a or 2b (0.196 – 1.0 mmol) [13][14], carbonyl compound 3 (1.0 equiv.), and TsOH (1.0 equiv.)
were mixed in a thick-walled tube. The mixture was vigorously stirred and heated up to 1008 in an oil
bath. The reaction progress was monitored by TLC and/or GC/MS. When two consecutive analyses
showed the same result, the mixture was cooled to r.t., and H2O (3 ml) was added. The resulting
suspension was neutralized with 0.4 ml of a 10% NaOH soln., stirred for 5 min, and then filtered. The
acquired solid was washed with H2O (3 ꢁ 6 ml) and dried at r.t. The crude product was obtained as a
colorless or pale-yellow crystalline powder, and was purified by CC.
Method B. In a thick-walled tube, 2a or 2b (0.196 – 0.392 mmol) and 3 (1.2 equiv.) were dissolved in
toluene (2 ml) at 1008. TsOH (1.1 equiv.) was added to the clear soln., and the mixture was vigorously
stirred until the TLC (or GC/MS) indicated completion of the reaction. The resulting suspension was
neutralized with 0.4 ml of a 10% NaOH soln. and stirred for 5 min. The mixture was extracted with Et2O
(5 ꢁ 10 ml), and the collected org. layers were dried (Na2SO4) and subsequently evaporated in vacuo to
obtain the crude product.
1-[2-Methyl-4-(tricyclo[3.3.1.13,7]dec-1-yl)quinolin-3-yl]ethanone (4a). Purified by CC (system B):
303 mg (95%; Method A, from 255 mg of 2a). Yellowish crystalline powder. M.p. 224 – 2278. Rf
(system A) 0.20. IR (KBr): 2988w, 2963w, 2900s, 2848m, 2680w, 1699s, 1566m, 1493w, 1455m, 1375m,
1
1314w, 1256w, 1200m, 1104w, 1052w, 961w, 869w, 760s, 684w, 655m, 576w, 535w. H-NMR: 1.86 (m, 3
CH2(Ad)); 2.19 (m, 3 CH(Ad)); 2.38 (m, 3 CH2(Ad)); 2.61 (s, MeꢀC(2)); 2.64 (s, COMe); 7.47 (dd, J ¼
7.6, HꢀC(6)); 7.64 (dd, J ¼ 7.3, HꢀC(7)); 8.07 (d, J ¼ 7.9, HꢀC(5)); 8.71 (d, J ¼ 8.6, HꢀC(8)). 13C-NMR:
24.0 (MeꢀC(2)); 29.3 (CH(Ad)); 35.8 (COMe); 36.8 (CH2(Ad)); 41.7 (C(Ad)); 43.0 (CH2(Ad)); 124.8
(CH); 125.1 (C); 127.8 (CH); 128.9 (CH); 130.3 (CH); 135.0 (C); 148.0 (C); 150.6 (C); 153.1 (C); 207.8
(C¼O). DI-MS: 319 (18, Mþ), 305 (23), 304 (100), 301 (9), 286 (6), 276 (8), 244 (6), 210 (7), 194 (6), 135
(26), 115 (6), 107 (6), 93 (13), 91 (8), 81 (5), 79 (17), 77 (9), 67 (8), 55 (7), 43 (14), 41 (9). ESI-MS: 661.3
(48, [2M þ Na]þ), 342.2 (12, [M þ Na]þ), 320.2 (100, [M þ H]þ). Anal. calc. for C22H25NO (319.44): C
82.72, H 7.89, N 4.38; found: C 83.05, H 7.83, N 4.21.
Ethyl 2-Methyl-4-(tricyclo[3.3.1.13,7]dec-1-yl)quinoline-3-carboxylate (4b). Purified by CC (sys-
tem B): 175 mg (50%; Method A, from 255 mg of 2a).Yellow crystalline powder. M.p. 105 – 1068. Rf
(system A) 0.29. IR (KBr): 2973m, 2917s, 2876m, 2853s, 1715s, 1570m, 1484m, 1460m, 1378m, 1302w,
1280m, 1215s, 1169m, 1094m, 1041m, 854w, 795w, 772s, 631w, 603w, 535w. 1H-NMR: 1.44 (t, J ¼ 6.9,
MeCH2); 1.87 (m, 3 CH2(Ad)); 1.93 (m, 3 CH(Ad)); 2.46 (m, 3 CH2(Ad)); 2.64 (s, MeꢀC(3)); 4.43 (q,
J ¼ 7.0, MeCH2); 7.44 (dd, J ¼ 7.3, HꢀC(6)); 7.62 (dd, J ¼ 7.3, HꢀC(7)); 8.03 (d, J ¼ 8.3, HꢀC(5)); 8.71 (d,
J ¼ 8.9, HꢀC(8)). 13C-NMR: 14.1 (MeCH2); 23.9 (MeꢀC(2)); 29.4 (CH(Ad)); 37.0 (CH2(Ad)); 41.6
(C(Ad)); 41.8 (CH2(Ad)); 61.7 (MeCH2); 124.5 (CH); 124.9 (C); 127.0 (C); 127.8, (CH); 128.8 (CH);
130.8 (CH); 148.7 (C); 151.1 (C); 155.0 (C); 171.9 (C¼O). GC/MS (tR 29.8 min): 350 (7), 349 (30, Mþ),
348 (8), 305 (23), 304 (100), 303 (12), 276 (7), 246 (6), 218 (6), 194 (5), 135 (22), 107 (8), 97 (6), 93 (14),
95 (5), 93 (13), 91 (13), 85 (6), 83 (6), 81 (8), 79 (15), 77 (8), 71 (8), 69 (9), 67 (10), 57 (13), 55 (13), 43
(8), 41 (10). ESI-MS: 721.3 (17, [2M þ Na]þ), 372.2 (10, [M þ Na]þ), 350.2 (100, [M þ H]þ). Anal. calc.
for C23H27NO2 (349.47): C 79.05, H 7.79, N 4.01; found: C 79.32, H 7.88, N 3.81.
Ethyl 4-(Tricyclo[3.3.1.13,7]dec-1-yl)quinoline-2-carboxylate (4c). Purified by CC (system A):
109 mg (33%; Method A, from 255 mg of 2a) or 45 mg (68%; Method B, from 50 mg of 2a). Colorless
crystalline powder. M.p. 100 – 1018. Rf (system A) 0.36. IR (KBr): 2976w, 2903s, 2846w, 1713s, 1583w,

Helvetica Chimica Acta – Vol. 95 (2012)
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1508w, 1477w, 1452w, 1369m, 1334m, 1310m, 1237s, 1154m, 1108m, 1023w, 973w, 930w, 882w, 781s, 633w.
1H-NMR: 1.49 (t, J ¼ 7.3, MeCH2); 1.89 (m, 3 CH2(Ad)); 2.23 (m, 3 CH(Ad)); 2.33 (m, 3 CH2(Ad)); 4.56
(q, J ¼ 7.3, MeCH2); 7.59 (dd, J ¼ 7.3, HꢀC(6)); 7.70 (dd, J ¼ 7.6, HꢀC(7)); 8.12(s, HꢀC(3)); 8.36 (d, J ¼
8.6, HꢀC(5)); 8.66 (d, J ¼ 8.9, HꢀC(8)). 13C-NMR: 14.6 (MeCH2); 29.2 (CH(Ad)); 37.0 (CH2(Ad)); 39.2
(C(Ad)); 42.3 (CH2(Ad)); 62.3 (MeCH2); 118.2 (CH); 126.3 (CH); 126.9 (CH); 128.3 (C); 128.8 (CH);
132.9 (CH); 148.2 (C); 149.1 (C); 157.3 (C); 166.2 (C¼O). GC/MS (tR 28.9 min): 291 (5), 264 (21), 263
(100), 149 (8), 135 (5), 93 (5), 79 (7), 57 (7), 43 (5), 41 (7). ESI-MS: 693.3 (100, [2M þ Na]þ), 374.2 (9,
[M þ K]þ), 358.2 (85, [M þ Na]þ), 336.3 (67, [M þ H]þ). Anal. calc. for C22H25NO2 (335.44): C 78.77, H
7.51, N 4.18; found: C 79.02, H 7.45, N 3.92.
1-[2-Phenyl-4-(tricyclo[3.3.1.13,7]dec-1-yl)quinolin-3-yl]ethanone (4d). Purified by CC (system A):
9 mg (6%; Method A, from 100 mg of 2a) or 50 mg (34%; Method B, from 100 mg of 2a). Pale yellow
crystalline powder. M.p. 177 – 1788. Rf (system B) 0.31. IR (KBr): 3045w, 3004w, 2966w, 2908s, 2860m,
1678s, 1593w, 1568w, 1556w, 1492w, 1450w, 1371w, 1317w, 1271w, 1221m, 1176w, 1161w, 918w, 866w, 768m,
723m, 694w, 598w. 1H-NMR: 1.73 (m, 3 CH2(Ad)); 2.06 (m, 3 CH(Ad)); 2.32 – 2.39 (overlapped m þ s, 3
CH2Ad, COMe); 7.48 – 7.78 (overlapped m, 7 H); 8.08 (d, J ¼ 5.9, HꢀC(5)); 8.79 (d, J ¼ 6.9, HꢀC(8)).
13C-NMR: 24.9 (COMe); 29.3 (CH(Ad)); 36.8 (CH2(Ad)); 41.9 (C(Ad); 43.0 (CH2(Ad)); 124.6 (CH);
124.9 (C); 128.0 (CH); 128.7 (CH); 129.1 (2 CH); 131.0 (CH); 131.8 (C); 133.7 (CH); 139.4 (C); 149.0
(C); 151.8 (C); 155.0 (C); 200.2 (C¼O). GC/MS (tR 45.5 min): 382 (13), 381 (44, Mþ), 380 (6), 364 (17),
306 (5), 305 (24), 304 (100), 303 (7), 276 (8), 231 (5), 230 (10), 218 (5), 135 (22), 107 (8), 106 (5), 105
(59), 93 (15), 91 (13), 81 (7), 79 (24), 78 (5), 77 (50), 67 (12), 55 (7), 41 (12). ESI-MS: 785.4 (5, [2M þ
Na]þ), 382.2 (100, [M þ H]þ). Anal. calc. for C27H27NO (381.51): C 85.00, H 7.13, N 3.67; found: C 85.27,
H 7.22, N 3.47.
2-Phenyl-4-(tricyclo[3.3.1.13,7]dec-1-yl)quinoline (4e). Purified by CC (system B): 150 mg (44%;
Method A, from 255 mg of 2a) or 64 mg (96%; Method B, from 50 mg of 2a). Yellow crystalline powder.
M.p. 127 – 1298. Rf (system A) 0.59. IR (KBr): 2903s, 2848m, 1686w, 1618w, 1587s, 1546m, 1493m, 1451m,
1341m, 1266w, 1180w, 1103w, 1078w, 994w, 897w, 870m, 769s, 756s, 689s, 675m, 629w, 578w, 545w.
1H-NMR: 1.94 (m, 3 CH2(Ad)); 2.27 (m, 3 CH(Ad)); 2.39 (m, 3 CH2(Ad)); 7.48 – 7.58 (overlapped m, 3 H
of Ph, HꢀC(6)); 7.69 (t, J ¼ 7.6, HꢀC(7)); 7.83 (s, HꢀC(3)); 8.18 (d, J ¼ 7.9, 2 Ho of Ph); 8.29 (d, J ¼ 8.3,
HꢀC(5)); 8.65 (d, J ¼ 8.6, HꢀC(8)). 13C-NMR: 29.3 (CH(Ad)); 37.2 (CH2(Ad)); 39.2 (C(Ad)); 42.5
(CH2(Ad)); 116.5 (CH); 124.8 (CH); 126.0 (C); 126.3 (CH); 127.8 (CH); 128.4 (CH); 129.0 (CH); 129.3
(CH); 131.9 (CH); 140.5 (C); 149.7 (C); 156.3 (C); 157.3 (C). GC/MS (tR 48.4 min): 340 (26), 339 (100,
Mþ), 338 (61), 296 (8), 283 (7), 282 (24), 244 (8), 243 (6), 232 (5), 230 (7), 219 (7), 203 (8), 152 (5), 135
(7), 91 (6), 79 (10), 77 (9), 67 (6), 41 (7). ESI-MS: 701.3 (16, [2M þ Na]þ), 362.2 (5, [M þ Na]þ), 340.2
(100, [M þ H]þ). Anal. calc. for C25H25N (339.47): C 88.45, H 7.42, N 4.13; found: C 88.21, H 7.49, N 3.95.
2-(4-Fluorophenyl)-4-(tricyclo[3.3.1.13,7]dec-1-yl)quinoline (4f). Purified by CC (system B): 44 mg
(31%; Method A, from 100 mg of 2a) or 67 mg (96%; Method B, from 50 mg of 2a). Colorless crystalline
powder. M.p. 160 – 1638. Rf (system A) 0.55. IR (KBr): 2905s, 2855w, 1586m, 1549w, 1501m, 1422w, 1341w,
1224m, 1154m, 898w, 839s, 758s, 723w, 670w, 620w. 1H-NMR: 1.92 (m, 3 CH2(Ad)); 2.25 (m, 3 CH(Ad));
2.37 (m, 6 CH(Ad)); 7.22 (dd, J ¼ 8.6, 2 CF¼CH); 7.50 (dd, J ¼ 7.3, HꢀC(6)); 7.67 (dd, J ¼ 7.6, HꢀC(7));
7.76 (s, HꢀC(3)); 8.14 – 8.23 (d, dd, 2 CF¼CHCH, HꢀC(5)); 8.27 (d, J ¼ 8.6, HꢀC(8)). 13C-NMR: 29.3
(CH(Ad)); 37.2 (CH2(Ad)); 39.2 (C(Ad)); 45.5 (CH2(Ad)); 115.9 (d, 2J(C,F) ¼ 88, CF¼CH); 116.1
(CH); 124.8 (CH); 126.0 (C); 126.3 (CH); 128.5 (CH); 129.6 (d, 3J(C,F) ¼ 31, CF¼CHCH); 131.8 (CH);
136.7 (d, 4J(C,F) ¼ 13, CH(Ph)); 149.9 (C); 156.2 (C); 156.4 (C); 163.9 (d, 1J(C,F) ¼ 1000, CF). DI-MS:
358 (26), 357 (100, Mþ), 356 (46), 314 (6), 302 (6), 301 (5), 300 (18), 262 (7), 261 (5), 248 (5), 237 (5),
135 (9), 93 (7), 79 (9), 67 (6), 55 (6), 41 (8). ESI-MS: 737.3 (18, [2M þ Na]þ), 380.2 (8, [M þ Na]þ), 358.2
(100, [M þ H]þ). Anal. calc. for C25H24FN (357.46): C 84.00, H 6.77, N 3.92; found: C 84.19, H 6.75, N
3.75.
2,3-Dihydro-9-(tricyclo[3.3.1.13,7]dec-1-yl)-1H-cyclopenta[b]quinoline (4g). Purified by CC (sys-
tem B): 75 mg (63%; Method A, from 100 mg of 2a). Yellowish crystalline powder. The sample
crystallized from CHCl3 was used for elemental analysis. M.p. 188 – 1918. Rf (system A) 0.15. IR (KBr):
2905s, 2850w, 1561w, 1497w, 1458w, 1223w, 1160w, 1029w, 1007w, 758s, 680w. 1H-NMR: 1.98 (m, 3
CH2(Ad)); 2.06 (m, CH2(2)); 2.19 (m, 3 CH(Ad)); 2.53 (m, 3 CH2(Ad)); 3.11 (t, J ¼ 7.9, CH2(1)); 3.52 (t,
J ¼ 7.3, CH2(3)); 7.40 (t, J ¼ 8.3, HꢀC(7)); 7.56 (t, J ¼ 7.6, HꢀC(6)); 8.07 (d, J ¼ 8.3, HꢀC(8)); 8.70 (d,

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Helvetica Chimica Acta – Vol. 95 (2012)
J ¼ 8.9, HꢀC(5)). 13C-NMR: 23.5 (CH2); 29.3 (CH(Ad)); 34.0 (CH2); 35.1 (CH2); 37.0 (CH2(Ad)); 42.7
(C(Ad)); 43.0 (CH2(Ad)); 124.3 (CH); 126.3 (C); 127.5 (CH); 128.3 (CH); 128.7 (CH); 128.9 (C); 133.0
(C); 146.4 (C); 167.7 (C). GC/MS (tR 27.0 min): 304 (24), 303 (100, Mþ), 302 (24), 259 (5), 247 (5), 246
(19), 208 (5), 207 (5), 206 (6), 204 (5), 194 (5), 167 (7), 135 (65), 107 (7), 93 (14), 91 (6), 81 (5), 79 (17),
77 (8), 67 (7), 55 (6), 41 (8). ESI-MS: 629.3 (44, [2M þ Na]þ), 326.2 (7, [M þ Na]þ), 304.2 (100, [M þ
H]þ). Anal. calc. for C23H26Cl3N (422.82): C 65.33, H 6.20, N 3.31; found: C 65.67, H 6.15, N 3.52.
1,2,3,4-Tetrahydro-9-(tricyclo[3.3.1.13,7]dec-1-yl)acridine (4h). Purified by CC (system B) 196 mg
(62%; Method A, from 255 mg of 2a). Yellow crystalline powder. M.p. 196 – 1998. Rf (system A) 0.21. IR
(KBr): 3007w, 2976w, 2923s, 2901s, 2847s, 1557w, 1490w, 1474w, 1454m, 1427w, 1387w, 1341w, 1304m,
1255w, 1167w, 110w, 911w, 757s, 679w, 621w. 1H-NMR: 1.77 – 1.91 (m, 3 CH2(Ad), CH2(6), CH2(7)); 2.18
(m, 3 CH(Ad)); 2.54 (m, 3 CH2(Ad)); 3.12 (t, J ¼ 6.6, CH2(8)); 3.22 (t, J ¼ 7.3, CH2(5)); 7.32 (dd, J ¼ 7.3,
HꢀC(2)); 7.50 (dd, J ¼ 7.3, HꢀC(3)); 7.96 (d, J ¼ 7.9, HꢀC(1)); 8.59 (d, J ¼ 8.9, HꢀC(4)). 13C-NMR: 21.4
(CH2); 22.9 (CH2); 29.7 (CH(Ad)); 30.9 (CH2); 33.6 (CH2); 37.2 (CH2(Ad)); 43.2 (C(Ad), CH2(Ad));
123.0 (CH); 126.6 (C); 126.9 (CH); 127.0 (CH); 129.6 (CH); 131.5 (C); 147.3 (C); 151.8 (C); 160.3 (C).
GC/MS (tR 31.1 min): 318 (18), 317 (74, Mþ), 316 (18), 260 (8), 136 (12), 135 (100), 107 (9), 93 (15), 91
(5), 79 (14), 77 (5), 67 (8), 55 (5), 41 (7). ESI-MS: 657.4 (7, [2M þ Na]þ), 318.2 (100, [M þ H]þ). Anal.
calc. for C23H27N (317.47): C 87.02, H 8.57, N 4.41; found: C 87.29, H 8.65, N 4.22.
7,8,9,10-Tetrahydro-11-(tricyclo[3.3.1.13,7]dec-1-yl)-6H-cyclohepta[b]quinoline (4i) Purified by CC
(system B): 68 mg (52%, Method A, from 100 mg of 2a). Colorless crystalline powder. M.p. 148 – 1508. Rf
(system a) 0.20. IR (KBr): 3053w, 3004w, 2907s, 2848s, 1557m, 1490m, 1453m, 1383m, 1342w, 1309w,
1252w, 963w, 757s, 623w. 1H-NMR: 1.81 – 1.94 (m, 3 CH2(Ad), CH2(7) – CH2(9)); 2.17 (m, 3 CH(Ad));
2.50 (m, 3 CH2(Ad)); 3.23 (m, CH2(6), CH2(9)); 7.31 (dd, J ¼ 7.8, HꢀC(2)); 7.49 (dd, J ¼ 7.4, HꢀC(3));
7.94 (d, J ¼ 8.3, HꢀC(1)); 8.51 (d, J ¼ 8.6, HꢀC(4)). 13C-NMR: 27.2 (CH2); 29.0 (CH2); 29.7 (CH(Ad));
31.0 (CH2); 32.3 (CH2); 37.2 (CH2(Ad)); 40.3 (CH2); 42.9 (C(Ad)); 43.2 (CH2(Ad)); 122.9 (CH); 126.7
(CH); 126.8 (C); 127.0 (CH); 129.7 (CH); 135.2 (C); 147.1 (C); 151.6 (C); 165.4 (C). GC/MS (tR
27.4 min): 332 (13), 331 (50, Mþ), 330 (12), 136 (11), 135 (100), 107 (7), 93 (13), 79 (13), 67 (7), 55 (5), 41
(6). ESI-MS: 685.4 (4, [2M þ Na]þ), 332.3 (100, [M þ H]þ). Anal. calc. for C24H29N (331.49): C 86.96, H
8.82, N 4.23; found: C 87.12, H 8.73, N 4.06.
6,7,8,9,10,11-Hexahydro-12-(tricyclo[3.3.1.13,7]dec-1-yl)cycloocta[b]quinoline (4j). Purified by CC
(system B): 60 mg (44%; Method A, from 100 mg of 2a) or 64 mg (95%, Method B, from 50 mg of 2a).
Fawn crystalline powder. M.p. 193 – 1948. Rf (system A) 0.35. IR (KBr): 3054w, 3009w, 2915s, 2846s,
1
1551m, 1490m, 1459m, 1439m, 1396w, 1342w, 1308m, 1159m, 1107m, 864w, 759s, 718w, 622w. H-NMR:
1.11 (m, CH2); 1.57 (m, CH2); 1.69 (m, CH2); 1.83 – 1.89 (m, 3 (CH2)Ad, CH2); 2.21 (m, 3 CH(Ad)); 2.60
(m, 3 CH2(Ad)); 3.25 (m, CH2(11)); 3.48 (m, CH2(6)); 7.35 (dd, J ¼ 7.3, HꢀC(2)); 7.52 (dd, J ¼ 7.6,
HꢀC(3)); 8.04 (dd, J ¼ 7.9, HꢀC(2)); 8.70 (d, J ¼ 8.9, HꢀC(4)). 13C-NMR: 24.9 (CH2); 26.8 (CH2); 27.7
(CH2); 29.8 (CH(Ad)); 31.8 (CH2); 34.2 (CH2); 37.2 (CH2(Ad)); 39.0 (CH2); 43.5 (C(Ad)); 44.1
(CH2(Ad)); 123.0 (CH); 126.8 (CH); 127.0 (C); 127.7 (CH); 130.7 (CH); 132.8 (C); 148.1 (C); 151.4 (C);
165.4 (C). GC/MS (tR 37.7 min): 346 (14), 345 (54, Mþ), 344 (29), 303 (12), 302 (8), 210 (34), 136 (11),
135 (100), 107 (9), 97 (5), 93 (17), 85 (5), 79 (17), 77 (5), 71 (6), 69 (9), 67 (10), 57 (12), 55 (11), 41 (10).
ESI-MS: 713.4 (4, [2M þ Na]þ), 346.3 (100, [M þ H]þ). Anal. calc. for C25H31N (345.52): C 86.90, H 9.04,
N 4.05; found: C 86.78, H 8.97, N 3.85.
6,7,8,9,10,11,12,13,14,15-Decahydro-16-(tricyclo[3.3.1.13,7]dec-1-yl)cyclododeca[b]quinoline (4k).
Purified by CC (system B) 30 mg (19%; Method A, from 100 mg of 2a) or 72 mg (92%, Method B,
from 50 mg of 2a). Colorless crystalline powder. M.p. 146 – 1488. Rf (system A) 0.52. IR (KBr): 2909s,
2846s, 1564w, 1550w, 1466m, 1440m, 1385w, 1386w, 1307w, 1245w, 1104w, 985w, 763s, 707w, 623w.
1H-NMR: 1.31 – 1.57 (m, 7 CH2); 1.82 – 1.97 (m, 3 CH2(Ad), CH2); 2.19 (m, 3 CH(Ad)); 2.55 (m, 3
CH2(Ad)); 3.05 (br. m, CH2(15)); 3.25 (m, CH2(6)); 7.33 (dd, J ¼ 8.3, HꢀC(2)); 7.49 (dd, J ¼ 7.3,
HꢀC(3)); 7.96 (d, J ¼ 8.3, HꢀC(1)); 8.64 (dd, J ¼ 8.9, HꢀC(4)). 13C-NMR: 23.0 (CH2); 23.6 (CH2); 25.9
(CH2); 27.7 (2 CH2); 27.8 (CH2); 29.2 (CH2); 29.3 (CH2); 29.8 (CH(Ad)); 31.7 (CH2); 35.7 (CH2); 37.2
(CH2(Ad)); 40.6 (C(Ad)); 43.5 (CH2(Ad)); 123.0 (CH); 126.8 (CH); 126.9 (CH); 127.2 (CH); 130.2 (C);
133.6 (C); 147.5 (C); 152.7 (C); 163.6 (C). DI-MS: 402 (14), 401 (61, Mþ), 400 (100), 386 (7), 330 (6), 317
(7), 316 (8), 290 (7), 267 (12), 266 (56), 194 (5), 135 (5), 93 (7), 81 (6), 79 (10), 67 (6), 55 (7), 41 (9).

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ESI-MS: 825.5 (4, [2M þ Na]þ), 402.3 (100, [M þ H]þ). Anal. calc. for C29H39N (401.63): C 86.72, H 9.79,
N 3.49; found: C 86.65, H 9.86, N 3.71.
5,6-Dihydro-7-(tricyclo[3.3.1.13,7]dec-1-yl)benzo[c]acridine (4l). Purified by CC (system B): 56 mg
(39%; Method A, from 100 mg of 2a) or 69 mg (96%; Method B, from 50 mg of 2a). White crystalline
powder. M.p. 210 – 2138. Rf (system A) 0.57. IR (KBr): 3012w, 2892s, 2852w, 1545w, 1491m, 1457w, 1382m,
1337w, 1103s, 1033w, 965w, 915w, 771s, 723s, 669w, 619m, 484w. 1H-NMR: 1.90 (m, 3 CH2(Ad)); 2.20 (m, 3
CH(Ad)); 2.55 (m, 3 CH2(Ad)); 2.80 (m, CH2(5)); 3.43 (m, CH2(6)); 7.25 (d, J ¼ 7.5, 1 H); 7.38(m, 2 H);
7.43 (dd, J ¼ 7.5, 1 H); 7.57 (dd, J ¼ 7.5, 1 H); 8.21 (br. s, 1 H); 8.42 (d, J ¼ 6.9, 1 H); 8.58 (d, J ¼ 8.7, 1 H).
13C-NMR: 28.6 (CH2); 29.6 (CH(Ad)); 31.2 (CH2); 37.1 (CH2(Ad)); 42.8 (CH2(Ad)); 43.2 (C(Ad));
123.6; 126.6; 126.7; 127.2; 127.2; 127.4; 127.4; 127.6; 129.5; 130.3; 135.4; 139.4; 147.6; 153.4. GC/MS (tR
51.0 min): 366 (14), 365 (47, Mþ), 308 (7), 254 (5), 136 (11), 135 (100), 107 (8), 93 (15), 81 (5), 79 (15), 67
(8), 41 (5). ESI-MS: 753.4 (5, [2M þ Na]þ), 388.2 (5, [M þ Na]þ), 366.3 (100, [M þ H]þ). Anal. calc. for
C27H27N (365.51): C 88.72, H 7.45, N 3.83; found: C 88.57, H 7.49, N 3.87.
3,4-Dihydro-9-(tricyclo[3.3.1.13,7]dec-1-yl)acridin-1(2H)-one (4m). Purified by CC (system A):
109 mg (84%; Method A, from 100 mg of 2a). Pale yellow crystalline powder. M.p. 191 – 1948. Rf
(system A) 0.19. IR (KBr): 2915s, 2901s, 2847m, 1671m, 1634w, 1563w, 1520s, 1481s, 1447s, 1417m, 1364s,
1338m, 1314m, 1189m, 1036w, 1000w, 853w, 762s, 615w, 567w. 1H-NMR: 1.83 (m, 3 CH2(Ad)); 2.14 (m, 3
CH(Ad)); 2.22 (m, CH2); 2.35 (m, 3 CH2(Ad)); 2.92 (m, CH2); 3.05 (m, CH2); 7.44 (br. s, HꢀC(7)); 7.64
(br. s, HꢀC(6)); 8.00 (d, J ¼ 6.3, HꢀC(8)); 8.60 (d, J ¼ 8.9, HꢀC(5)). 13C-NMR: 20.9 (CH2); 29.5
(CH(Ad)); 34.1 (CH2); 36.9 (CH2(Ad)); 40.7 (CH2); 42.4 (C(Ad)); 42.9 (CH2(Ad)); 124.1 (CH); 127.4
(CH); 127.6 (C); 129.6 (2 CH); 132.4 (C); 148.2 (C); 160.0 (C); 160.3 (C); 205.5 (C¼O). DI-MS: 332
(12), 331 (51, Mþ), 330 (52), 316 (13), 314 (14), 313 (8), 304 (23), 303 (100), 258 (5), 256 (5), 248 (5), 246
(5), 234 (5), 232 (5), 223 (5), 222 (9), 220 (6), 218 (5), 204 (5), 182 (5), 180 (6), 167 (5), 135 (6), 128 (5),
127 (5), 93 (9), 92 (5), 91 (7), 83 (5), 81 (5), 79 (13), 77 (7), 69 (5), 67 (8), 57 (11), 55 (13), 43 (9), 41
(14). ESI-MS: 685.3 (16, [2M þ Na]þ), 332.2 (100, [M þ H]þ). Anal. calc. for C23H25NO (331.45): C 83.34,
H 7.60, N 4.23; found: C 83.08, H 7.45, N 4.16.
2-Phenyl-4-[(tricyclo[3.3.1.13,7]dec-1-yl)methyl]quinoline (4n). Purified by CC (system B): 28 mg
(22%; Method A, from 100 mg of 2b). Yellow crystalline powder. M.p. 164 – 1688. Rf (system A) 0.36. IR
(KBr): 3060w, 2903s, 2846s, 1590s, 1546s, 1493m, 1451m, 1412w, 1343m, 1310w, 1232w, 1102w, 1031w,
887w, 771s, 768s, 692s, 586w, 542w. 1H-NMR: 1.56 – 1.70 (overlapped m, 6 CH2(Ad)); 1.96 (m, 3 CH(Ad));
2.97 (s, AdCH2); 7.47 – 7.58 (overlapped m, 4 H); 7.63 (s, HꢀC(3)); 7.71(dd, J ¼ 7.7, HꢀC(7)); 8.12 – 8.23
(overlapped m, 4 H). 13C-NMR: 29.0 (CH(Ad)); 35.1 (C(Ad)); 37.0 (CH2(Ad)); 43.3 (CH2(Ad)); 46.4
(AdCH2); 121.8 (CH); 125.1 (CH); 125.8 (CH); 126.7 (C); 127.8 (CH); 128.3 (CH); 129.0 (CH); 129.3
(CH); 129.4 (CH); 130.5 (C); 139.2 (C); 150.6 (C); 156.4 (C). GC-MS (tR 61.9 min): 353 (11, Mþ), 136
(11), 135 (100), 107 (7), 93 (13), 79 (15), 77 (5), 67 (6). ESI-MS: 729.4 (5, [2M þ Na]þ), 376.3 (6, [M þ
Na]þ), 354.3 (100, [M þ H]þ). Anal. calc. for C26H27N (353.50): C 88.34, H 7.70, N 3.96; found: C 88.21, H
7.63, N 3.81.
3,4-Dihydro-9-[(tricyclo[3.3.1.13,7]dec-1-yl)methyl]acridin-1(2H)-one (4o). Purified by CC (sys-
tem A): to yield 40 mg (31%; Method A, from 100 mg of 2b). Yellow crystalline powder. M.p. 163 – 1668.
Rf (system A) 0.13. IR (KBr): 2904s, 2847m, 1704s, 1650m, 1579m, 1497m, 1455w, 1371m, 1308w, 1220s,
1161s, 1125s, 1085w, 1029s, 1007s, 976w, 817m, 772m, 682s, 658w, 570s. 1H-NMR: 1.35 – 1.61 (overlapped
m, 6 CH2(Ad)); 1.85 (m, 3 CH(Ad)); 2.20 (m, CO(CH2)2CH2); 2.79 (m, COCH2CH2CH2); 3.08 (d, J ¼
13.0, 1 H AdCH2); 3.25 (m, COCH2(CH2)2); 4.41 (d, J ¼ 13.0, 1 H, AdCH2); 7.49 (dd, J ¼ 7.9, HꢀC(7));
7.72 (dd, J ¼ 7.6, HꢀC(6)); 8.00 (d, J ¼ 8.1, HꢀC(8)); 8.22 (d, J ¼ 8.4, HꢀC(5)). 13C-NMR: 21.3 (CH2); 29.1
(CH(Ad)); 34.8 (CH2); 36.7 (C(Ad)); 36.9 (CH2(Ad)); 38.4 (CH2); 41.4 (CH2); 43.1 (CH2(Ad)); 125.8
(CH); 127.1 (CH); 127.8 (C); 128.8 (C); 129.0 (CH); 131.3 (CH); 148.0 (C); 149.7 (C); 161.3 (C); 202.0
(C¼O). DI-MS: 345 (9, Mþ), 136 (11), 135 (100), 107 (7), 93 (11), 79 (12), 67 (6), 57 (5), 55 (5), 41 (5).
ESI-MS: 713.3 (5, [2M þ Na]þ), 368.2 (4, [M þ Na]þ), 346.2 (100, [M þ H]þ). Anal. calc. for C24H27NO
(345.48): C 83.44, H 7.88, N 4.05; found: C 83.68, H 7.89, N 3.96.
Data of 4o · TsOH. M.p. > 2308. 1H-NMR: 1.35 – 1.65 (m, 6 CH2(Ad)); 1.91 (m, 3 CH(Ad)); 2.30 (m,
CO(CH2)2CH2); 2.37 (s, MePh); 2.87 (m, COCH2CH2CH2); 3.23 (d, J ¼ 12.0, 1 H, AdCH2); 3.78 (m,
COCH2(CH2)2); 4.67 (d, J ¼ 12.0, 1 H AdCH2); 7.21 (d, J ¼ 7.8, 2 H of Ph); 7.82 (dd, J ¼ 7.6, HꢀC(7)); 7.90
(d, J ¼ 7.8, 2 H of Ph); 8.04 (dd, J ¼ 7.7, HꢀC(6)); 8.42 (d, J ¼ 8.3, HꢀC(8)); 8.72 (d, J ¼ 8.6, HꢀC(5)).

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Helvetica Chimica Acta – Vol. 95 (2012)
13C-NMR: 20.4 (Me); 21.5 (CH2); 29.1 (CH(Ad)); 29.7 (CH2); 36.5 (CH2); 38.5 (C(Ad)); 39.9 (CH2);
40.6 (CH2(Ad)); 43.3 (CH2(Ad)); 122.5 (C); 126.3 (CH); 127.5 (CH); 127.7 (CH); 129.0 (CH); 129.1
(CH); 129.2 (C); 136.4 (CH); 138.2 (C); 140.3 (C); 142.7 (C); 159.3 (C); 161.3 (C); 202.0 (C¼O). Anal.
calc. for C31H35NO4S (517.68): C 71.92, H 6.81, N 2.71, S 6.19; found: C 72.23, H 6.72, N 2.89, S 5.83.
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Received November 8, 2011