Cyclisation reactions of N-cinnamoyl-9-aminoanthracenes

Article abstract of DOI:10.1039/c4ob00411f

N-Cinnamoyl-9-aminoanthracenes cyclise with PPA or triflic acid to form novel 2-azahexacyclo[10.6.6.0^1,5.0^6,11.0 ^13,18.0^19,24]tetracosa-6(11),7,9,13,15,17,19(24),20,22- nonaen-3-ones. In contrast, both N-cinnamo

Full text of DOI:10.1039/c4ob00411f

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Cyclisation reactions of N-cinnamoyl-9-
aminoanthracenes†
Cite this: Org. Biomol. Chem., 2014,
12, 3211
Frank D. King,* Abil Aliev, Stephen Caddick and Derek Tocher
Received 22nd February 2014,
Accepted 1st April 2014
N-Cinnamoyl-9-aminoanthracenes cyclise with PPA or triflic acid to form novel 2-azahexacyclo-
[10.6.6.01,5.06,11.013,18.019,24]tetracosa-6(11),7,9,13,15,17,19(24),20,22-nonaen-3-ones. In contrast, both
N-cinnamoyl-N-methyl-9-(2-aminomethyl)anthracene and N-cinnamoyl-9-(2-aminoethyl)anthracene
undergo an intramolecular Diels–Alder cycloaddition.
DOI: 10.1039/c4ob00411f
www.rsc.org/obc
pated that we would get novel products from either Diels–
Alder or carbocation addition to the central ring.
Introduction
An amine and one or more aryl groups are key structural fea-
tures of many modulators of G-protein coupled receptors. We
are therefore interested in approaches to the synthesis of
structures which have a unique special disposition of these
functional groups to identify more potent and selective modu-
lators. We have recently reported that the triflic acid-mediated
cyclisation of N-cinnamoyl-anilines1 and N-cinnamoyl-
naphthylamines2 give novel azacycles. For example, N-benzyl-
N-cinnamoyl-1-naphthylamines 1 cyclise to give the polycyclics
2 (Scheme 1).2
In this paper, we report the results obtained from an
investigation into the cyclisation of N-cinnamoyl-9-aminoan-
thracenes and homologues. Anthracenes have a very reactive
central ring. For example, 9-amidoanthracenes are known to
act as dienes in Diels–Alder cycloadditions3 and nitration in
HCl gives the 9-nitro-10-chloro addition product.4 Therefore,
by analogy with the cinnamoyl-naphthylamines, we antici-
Results and discussion
The N-cinnamoyl-9-aminoanthracenes 3a, 3e, 3g, 3i, 3k and 3m
were prepared from 9-aminoanthracene4 and the appropriate
cinnamoyl chloride with N,N-dimethylaniline as base. The
required products formed as precipitates, which were collected
and dried. Further product could be obtained from the mother
liquors by column chromatography. The N-substituted ana-
logues 3b–d and 3f, 3h, 3j, 3l and 3n were readily prepared
by N-alkylation with the appropriate iodide or bromide with
KOt-Bu as base.
The NH-amides 3a, 3e, 3g, 3i, 3k and 3m were found to be
very insoluble in a wide range of solvents. However, recrystallisa-
tion was possible from DMSO–water. Considering the structure
of these amides, the NMR of 3a at room temperature showed a
symmetry about the anthracene, with no evidence of rotamers
in DMSO-d6. In contrast, despite its low solubility in CDCl3, two
sets of peaks were observed in CDCl3 solution with the ratio of
3 : 2. Exchange cross-peaks were observed in NOESY spectra,
confirming that the observed two sets of peaks are due to two
rotamers. The largest chemical shift difference was observed
for the COCHvC proton resonating at 6.95 ppm in the major
rotamer and at 5.91 ppm in the minor rotamer. Therefore, we
concluded that the structure of the major rotamer has the
expected syn relationship of the amide carbonyl5 (Fig. 1A), with
the amide plane orthogonal to the plane of the anthracene.
This conformation would minimise the steric interactions
between the amide carbonyl and COCHvC proton, and the
1,8 protons of the anthracene. The upfield shift of the
COCHvC proton in the minor conformer is due to the ring
current effect6 and suggests that this proton is placed above
the anthracene ring, in agreement with structure B in Fig. 1.
Ring current effects are relatively strong and are felt at rela-
Scheme 1 TfOH-mediated cyclisation of N-benzyl-N-cinnamoyl-1-
aminonaphthalenes.
Department of Chemistry, University College London, 20 Gordon Street, London, UK.
E-mail: fd.king@btinternet.com
†Electronic supplementary information (ESI) available. CCDC 958857 and
984577. For ESI and crystallographic data in CIF or other electronic format see
DOI: 10.1039/c4ob00411f
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TfOH (10 equiv.) in CHCl3 (Table 1, entry 1) gave a trace of a
less polar product, which under UV light showed as a bright
blue fluorescent spot, and a more polar product that was weak
when viewed under UV light, but reacted strongly with KMnO4.
On purification by column chromatography on SiO2, the small
amount of the less polar product could not be obtained in
pure form. However, the more polar major product (69% yield)
was found to be the 9,10 addition product 4a (Scheme 2).
1
The structure was assigned by H and 13C NMR. In particu-
Fig. 1 DFT-optimised geometries of two rotamers of 3a.
lar, in the 1H NMR spectrum, there were four aliphatic
protons, three mutually coupled doublet of doublets and a
singlet at δ 4.96, and twelve aromatic protons. In the 13C NMR
spectrum, four aliphatic C signals were observed, a CH2, two
CH and a C, consistent with the proposed structure, which was
tively long distances of >4 Å.6 Therefore, the change in chemi-
cal shift of the ortho-Ph protons from 7.65 ppm in the major
rotamer to 7.08 ppm in the minor rotamer is also in agreement
with structures A (major) and B (minor) shown in Fig. 1. The
NMR spectra of the N-alkyl derivatives 3b–d showed symmetry
similar to that in 3a, but with a large upfield shift of the
COCHvC cinnamoyl proton to δ 5.82–5.87 ppm in 3b–d. As
discussed above for rotamer 3a–B, this is consistent with a
shielding ring current effect when the proton is placed above
the aromatic ring.6 For the N-benzyl 3d, NOEs were observed
between the COCHvC proton and the 1,8 protons of the
anthracene, and the COCHvCH proton and the ortho protons
of the cinnamoyl phenyl. No NOE was observed with the
benzylic CH2, which itself showed NOE’s with the 1,8-protons
of the anthracene and the ortho protons of the benzyl phenyl.
Thus, we believe that the structure of the N-alkyl derivatives
also have the amide group orthogonal to the plane of the
anthracene, but with the anthracene anti to the carbonyl and
the alkyl group syn. This would place the COCHvC proton
over the top of the anthracenyl central ring (Fig. 1B). The con-
formation of the amide in rotamer B would be that required
for a cyclo-addition reaction.
1
further verified using two- and three-bond H–13C correlations
in the HMBC spectrum.
The results from the acid-mediated cyclisation reactions are
shown in Table 1. From TLC, the initial reaction of 3a with Scheme 2 Proposed mechanism of formation of 4a.
Table 1 Acid-mediated cyclisation of N-cinnamoyl-9-aminoanthracenes 3a–d
Entry
Amide
R
Solvent
Acida
Temp. (°C)
Time (h)
Product
R
Yield (%)
1
2
3
4
5
6
7
8
3a
3a
3a
3a
3b
3b
3c
3d
H
H
H
H
Me
Me
Et
CHCl3
—
—
PhCl
CHCl3
—
TfOH
PPA
CSA
AlCl3
TfOH
PPA
65
120
120
25
3
2
5
24
2
2
4a
4a
4a
4a
4b
4b
4c
4d
H
H
H
H
Me
Me
Et
69
78
0
0
65
92
89
90
88
120
120
120
—
—
PPA
PPA
2
2
PhCH2
PhCH2
a TfOH: triflic acid; PPA: polyphosphoric acid; CSA: (+)10-camphorsulfonic acid.
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Other acids were investigated and PPA was found to give a
The N-methyl 3b gave excellent yields of the 9,10 addition
superior yield of 4a (78% yield). However, neither (+)10- product 4b with both TfOH (92% yield) and PPA (89% yield).
camphorsulfonic acid nor AlCl3 gave any 4a. The former gave The NMR of 4b was similar to that of 4a and the structure was
recovered starting material and the latter a black insoluble confirmed by X-ray crystallographic analysis (Fig. 2). With PPA,
material. By analogy with the reaction with N-benzyl-N-cinna- both the N-ethyl 3c and N-benzyl 3d also gave excellent yields
moyl-1-amino-naphthalenes,2 we believe that the acid doubly of 9,10 addition products 4c and 4d (both 90% yield). The
protonates the cinnamoyl group to form a benzylic carbo- presence of the N-alkyl group appears to inhibit the formation
cation, which adds to the 9 position to form a spiro intermedi- of the less polar by-product seen with 4a.
ate, with the carbocation now located at the 10 position, close
to the phenyl group, which facilitates ring closure (Scheme 2).
The effect of substituents in the cinnamoyl group was
investigated and the results are summarised in Table 2.
N-Benzyl derivatives were also investigated because, on
reduction to the amine, the benzyl group should be readily
removable by catalytic hydrogenation.7 The results for 3a and
3d are included for comparison. With PPA, the 4-methyl
derivatives 3e and 3f (Table 2, entries 2 and 3) gave excellent
yields of the 9,10 addition products 4e and 4f respectively.
However, the reaction of the 4-chloro 3g (entry 5) gave con-
siderable amounts of a black insoluble material and only a
modest yield of the 9,10 addition product 4g was obtained
(36% yield). With TfOH (entry 6), less insoluble material was
formed, however 4f was still only obtained in a moderate yield.
In both cases, considerably more of the less polar by-product
was obtained (20% yield in both cases), which was found to be
the product 7 derived from cyclisation onto the 1 position of
the anthracene.
Fig. 2 Structure of 4b as determined by X-ray structure crystallography.
ORTEP diagram (50% probability ellipsoids) showing the crystallographic
atom numbering scheme. Cambridge Crystallographic Data Centre
deposition number CCDC 958857.
Table 2 Acid-mediated cyclisation of N-cinnamoyl-9-aminoanthracenes 3e–n
Entry
Amide
R
R′
Acida
Temp. (°C)
Time (h)
Product
R
Yield (%)
1
2
3
4
5
6
7
8
3a
3d
3e
3f
3g
3g
3h
3h
3i
3j
3j
3j
3k
3k
3k
3l
3l
3m
3n
H
H
4-Me
4-Me
4-Cl
4-Cl
4-Cl
4-Cl
4-CF3
4-CF3
4-CF3
4-CF3
4-OMe
4-OMe
4-OMe
4-OMe
4-OMe
3-Me
3-Me
H
CH2Ph
H
CH2Ph
H
H
CH2Ph
CH2Ph
H
CH2Ph
CH2Ph
CH2Ph
H
PPA
PPA
PPA
PPA
PPA
TfOH
PPA
TfOH
PPA
PPA
TfOH
TfOH
PPA
TfOH
TfOH
TfOH
CSA
120
120
120
120
120
65
120
65
120
120
65
135
120
65
25
25
2
2
2
2
2
4
8
4
8
8
8
8
1
0.25
1
1
8
4a
4d
4e
4f
4g
4g
4h
4h
4i
4j
4j
4j
4k
4k
4k
4l
4l
4m
4n
H
H
9-Me
9-Me
9-Cl
9-Cl
9-Cl
9-Cl
9-CF3
9-CF3
9-CF3
9-CF3
9-OMe
9-OMe
9-OMe
9-OMe
9-OMe
8-Me
8-Me
78
90
84
88
36
44
45
70
0
0
0
0
31
46
58
77
0
73
87
9
10
11
12
13
14
15
16
17
18
19
H
H
CH2Ph
CH2Ph
H
135
120
120
PPA
PPA
2
2
CH2Ph
a TfOH: triflic acid; PPA: polyphosphoric acid; CSA: (+)10-camphorsulfonic acid.
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nitrovinyl)anthracene,11 followed by acylation with cinnamoyl
chloride. Previously, the use of LAH had been reported, but no
yield of the amine was quoted.12 Reaction of 8 with TfOH gave
no identifiable products. However, with PPA the product
obtained was the Diels–Alder adduct 9 (96% yield). The same
product was obtained in similar yield simply by heating 8 in
chlorobenzene. However, the reaction in chlorobenzene was
slower (4 h vs. 30 min). In both cases, the expected trans stereo-
We believe that the electron withdrawing nature of the chlor- chemistry was obtained.15 The NMR assignments for 9 are
ine reduces the rate of the final carbocation cyclisation 6 → 4a included in Table 3. The NMR spectrum in the aliphatic
(Scheme 2). This result is also consistent with the formation of region clearly showed a –CH2–CH2– and a separate –CH–CH–
the spiro carbocation 6 being reversible, in equilibrium with CH– arrangement. In the carbon spectrum there was also an
the carbocation 5. This could then undergo the alternative, aliphatic, tetra-substituted C at δ 44.83, a mono-substituted
less favoured cyclisation to give 7, analogous to that previously phenyl and two 1,2-disubstituted phenyls. The bicyclo[2.2.2]-
observed with the N-cinnamoyl-naphthylamines.2 N-alkylation octane unit, formed by carbons 15a, 12a, 11, 10a, 7a, 4, 3 and
would be expected to inhibit this reaction due to a steric inter-
action with the 8-proton of the anthracene. In agreement with
Table 3 1H and 13C NMR assignments for ( )9. The optimised geometry
(below) and calculated J couplings (in brackets) are also shown
this, cyclisation of the N-benzyl derivative 3h with TfOH gave a
good yield of product 4h (entry 8), better than with PPA (entry
7), with little formation of the N-benzyl analogue of 7.
With the much more electron withdrawing CF3 substituent
(entries 9–12), no cyclisation was observed and starting
material was recovered. With the 4-methoxy compound 3k,
only moderate yields of 4k were obtained with both PPA (entry
13) and TfOH (entry 14) under the normal heated conditions.
However, with TfOH at room temperature, 3k rapidly reacted
to give a slightly better yield of 4k (entry 15). Similarly the
N-benzyl derivative 3l rapidly cyclised with TfOH at room
temperature to give a good yield of 4l (entry 16). For both 3m
(entry 17) and 3n (entry 18), only single regioisomers, 4m and
4n respectively, were formed in good yields. NMR analysis
showed that they were the products derived from cyclisation
onto the less sterically hindered 6-position, para to the methyl.
This result was surprising, as in a previous study on the TfOH-
mediate iminium ion cyclisation onto a meta-methyl substi-
tuted phenyl, a mixture of isomers derived from cyclisation
onto both the ortho and para positions was obtained.8 Similar
electrophilic reactions, such as nitration, of meta-xylene give
mixtures of products.9 However, on examination of molecular
models, it appears that the product derived from cyclisation
onto the ortho position of the meta-substituted phenyl would
have a severe steric clash between the 10-methyl group and the
12-CH proton.
The cyclisation reaction to form the polycyclics could theor-
etically be reversible. If the reaction were reversible, heating
the polycyclics with TfOH in benzene should re-form the
initial carbocation 5 (Scheme 2), which would be trapped by
the solvent to form the 3,3-diphenylpropionamide.10 However,
on heating the polycyclics 4a and 4d with TfOH in benzene at
reflux for 18 h, no reaction was observed and starting material
was recovered in both cases. Thus it would appear that the
cyclisation reaction is essentially irreversible.
The investigation of homologated cinnamamides was then
undertaken to see if 6- and 7-membered spiro compounds
could be formed. The aminoethyl analogue 8 was prepared in
a 68% yield by a one-pot procedure via alane reduction of 9-(2-
Coupled
protons
Proton
δ/ppm
J/Hz
6.3 (5.1)
−14.1 (−13.2)
11.7 (11.2)
7.9 (7.7)
6.1 (5.7)
1.9 (0.9)
−12.4 (−11.6)
2.3 (2.4)
3
2.66
2.88
3.12
3.72
3.85
4.09
4.20
5.84
6.76
7.04
7.08
7.12
7.13
7.13
7.14
7.22
7.31
7.33
7.40
3,16
5a
5e
6e
16
6e
11
NH
18
12
13
8
5a,5e
5a,6a
5a,6e
5e,6a
5e,6e
̲
6a,6e
11,16
12,13
12,14
13,14
13,15
14,15
7.3 (6.5)
1.4 (0.9)
7.3 (6.6)
1.2 (0.8)
9
7.6 (6.7)
20
19
14
15
10
7
Carbon
δ/ppm
Carbon
δ/ppm
5-CH2
6-CH2
3-CH
23.89
39.25
54.14
44.83
48.51
51.82
119.79
122.04
124.02
125.79
125.92
14-CH
20-CH
9-CH
12-CH
18-CH
19-CH
7a-C
12a-C
17-C
15a-C
10a-C
2-CvO
126.06
126.47
126.52
126.62
128.04
128.23
140.23
141.59
144.29
145.98
146.31
172.81
4-C
16-CH
11-CH
15-CH
7-CH
10-CH
8-CH
13-CH
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16, is a rigid structure and the coupling between the 3-H and with either TfOH or PPA, although the starting material
16-H of 6.3 Hz is consistent with a trans orientation. There is rapidly disappeared. We believe that the anthracenylmethyl
also a strong NOE observed between the signals for the 3-H group is rapidly cleaved due to the high stability of the
and the 18-H protons, consistent with them being cis.
9-anthracenylmethyl carbocation.13 Indeed, 9-anthracenyl-
methyl has been used as an acid-cleavable protecting group for
phenols.14 However, on heating in chlorobenzene, 10 gave an
excellent yield of the Diels–Alder product 11. The structure of
11 was assigned by NMR spectral comparison with 9.
Based upon the NMR studies and using a DFT geometry
optimisation, the solution phase structure of 9 (A) is shown in
Fig. 3 together with the ORTEP (50% probability ellipsoids)
diagram (B) from the X-ray crystal structure analysis.
Summary and conclusion
The anthracenylmethyl homologue 10, prepared from the
commercially available amine, gave no identifiable product
We have shown that both N-cinnamoyl-9-aminomethyl- and
N-cinnamoyl-9-aminoethyl-anthracenes give Diels–Alder cyclo-
addition products on heating. However, N-cinnamoyl-9-amino-
anthracenes cyclise with either PPA or TfOH to give the novel
polycyclic
2-azahexa-cyclo[10.6.6.01,5.06,11.013,18.019,24]-tetra-
cosa-6(11),7,9,13,15,17,19(24),20,22-nonaen-3-ones in moder-
ate to good yields. We believe that protonation of the
cinnamoyl group forms a benzylic carbocation, which adds to
the 9-position of the anthracene to give a doubly benzylic-
stabilised carbocation at the 10 position. This then undergoes
an electrophilic ring closure onto the phenyl of the cinnamoyl
group. The cyclisation reaction is facilitated by electron donat-
ing groups on the phenyl ring. In most cases, for NH cinnam-
amides, a small amount of by-product is formed via cyclisation
onto the 1-position of the anthracene. N-alkylation inhibits
this side reaction. Only with a mildly electron withdrawing
group on the cinnamoyl moiety is this by-product formed in
sufficient quantity to be isolated, purified and characterised.
However, no cyclisation is observed with strongly electron with-
drawing substituents. We believe that the 9-aminoanthracenes
do not undergo the Diels–Alder cycloadditions because
the resultant spiro-azetidinones would be too strained to be
thermo-dynamically favoured.
Experimental
All reagents were commercially available, unless otherwise
specified, and used without purification. The chloroform used
was stabilized with amylene. Petroleum ether was the 40–60 °C
fraction. Infrared spectra were run neat on a Perkin Elmer 100
FT IR spectrometer. Solution 1H and 13C NMR spectra were
recorded on a Bruker NMR spectrometer DRX500 or Avance III
600 equipped with z-gradient facilities. 1H and 13C chemical
shifts are given relative to TMS. Unless otherwise specified,
Fig. 3 Solution phase structure of (19S,20R) 9 from NMR studies (A)
and (B), an ORTEP diagram of (19R,20S) 9 (50% probability ellipsoids)
from X-ray structure crystallography. Cambridge Crystallographic Data
Centre deposition number CCDC 984577.
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spectra were recorded at 25 °C. NMR J-couplings were pre- (CH3), 120.5 (CH), 123.9 (CH), 125.6 (CH), 125.9 (CH), 126.0
dicted using calculations based on density functional theory (CH), 126.8 (CH), 127.8 (CH), 127.9 (C), 128.4 (CH), 129.6 (CH),
(DFT), as described in detail previously.16 Geometry optimis- 129.7 (CH), 131.3 (C), 132.1 (C), 133.8 (C), 134.6 (CH), 139.7
ations were carried using M06-2X/6-31+G(d) level of theory. (C), 140.4 (CH), 165.3 (C); FTIR (solid) ν = 3245, 1649, 1613,
Mass spectra were run on a Thermo Mat900XP. Melting points 1499, 1333, 1191, 975, 815, 731 cm−1; MS (EI) m/z (%) 337 (M+,
were determined on a Sanyo-Gallenkamp capillary melting 57), 193 (94), 145 (60), 86 (69), 85 (100); HMRS (EI): m/z calcd
point apparatus and are uncorrected.
for C24H19NO [M+] 337.1467, found 337.1460.
N-(4-Chlorocinnamoyl)-9-aminoanthracene 3g. Isolated as a
yellow solid (84% yield); mp >310 °C; 1H NMR (600 MHz,
DMSO-d6) δ 7.21 (1H, d, J = 15.8 Hz), 7.53–7.70 (7H, m), 7.67
General procedure for the synthesis of N-cinnamoyl-9-
aminoanthracenes
A suspension of the appropriate acid (2.5 g, 15 mmol), oxalyl (1H, d, J = 15.8 Hz), 7.76 (2H, d, J = 8.3 Hz), 8.05–8.08 (2H, m),
chloride (1.4 mL, 16 mmol) and DMF (2 drops) in DCM 8.13–8.16 (2H, m), 8.63 (1H, s), 10.51 (1H, s); 13C NMR
(50 mL) was stirred at ambient temperatures until evolution of (150.1 MHz, DMSO-d6) δ 122.4 (CH), 123.9 (CH), 125.6 (CH),
CO2 had ceased (about 2 h). CHCl3 (50 mL) was added and the 126.0 (CH), 126.1 (CH), 127.9 (C), 128.5 (CH), 129.1 (CH), 129.4
solvent removed by rotary evaporation. The residue was dis- (C), 129.6 (CH), 131.3 (C), 133.8 (C), 134.3 (C), 139.0 (CH),
solved in EtOAc (20 mL) and added to a stirred solution of 164.9 (C); FTIR (solid) ν = 3244, 1650, 1615, 1504, 1206, 1093,
9-aminoanthracene4 (2.9 g, 15 mmol) and N,N-diethylaniline 973, 822, 730 cm−1; MS (EI) m/z (%) 359 (M+, 10), 357 (M+, 31),
(2.5 mL, 20 mmol) in EtOAc (100 mL), then heated to 60 °C for 193 (100), 165 (47); HMRS (EI): m/z calcd for C23H16ClNO [M+]
1 h. On cooling to 0 °C, the solid product was collected, 357.0924, found 357.0934.
washed with EtOAc (2 × 20 mL) and dried. The product was
N-(4-Trifluoromethylcinnamoyl)-9-aminoanthracene 3i. Iso-
used for reactions without further purification, although a lated as a yellow solid (75% yield); mp 296 °C; 1H NMR
small amount was recrystallised from DMSO–EtOH for charac- (600 MHz, DMSO-d6) δ 7.30 (1H, d, J = −15.9 Hz), 7.50–7.58
terization purposes. Additional product was obtained by (4H, m), 7.71 (1H, d, J = 15.9 Hz), 7.82 (2H, d, J = 8.1 Hz), 7.93
washing the EtOAc mother liquors with 1 M HCl (2 × 50 mL), (2H, d, J = 8.0 Hz), 8.02 (2H, d, J = 7.7 Hz), 8.13 (2H, dd, J = 1.8,
water (2 × 50 mL), 1 M NaOH (1 × 50 mL), brine (50 ML), 8.1 Hz), 8.61 (1H, s), 10.89 (1H, s); 13C NMR (150.1 MHz,
drying (MgSO4), concentration in vacuo and purification by DMSO-d6) δ 124.0 (CH), 124.1 (CH), 124.5 (C, q, J = 272 Hz),
flash column chromatography on SiO2, the product eluting 124.6 (C), 124.7 (CH), 126.1 (CH), 126.3 (CH), 126.7 (CH), 128.2
with DCM to 2% MeOH–DCM, depending upon the polarity. (C), 128.8 (CH), 128.9 (CH), 129.4 (CH), 129.9 (C, q, J = 32 Hz),
Quoted yields are that of the combined quantities.
131.6 (C), 139.2 (CH), 139.3 (C), 165.3 (C); F NMR (376.4 MHz,
N-Cinnamoyl-9-aminoanthracene 3a. Isolated as a yellow DMSO-d6) δ = −61.15; FTIR (solid) ν = 3245, 1653, 1614, 1504,
solid (78% yield); mp >310 °C; 1H NMR (600 MHz, CDCl3), 1324, 1169, 1116, 1067, 835, 734 cm−1; MS (EI) m/z (%) 391
Rotamer A: δ 6.95 (1H, d, J = 15.6 Hz, COCH), 7.44 (1H, m, (M+, 92), 199 (32), 193 (100; HMRS (EI): m/z calcd for
p-Ph), 7.45 (2H, m, m-Ph), 7.49 (2H, m, H-3,6), 7.54 (2H, m, C24H16F3NO [M+] 391.1184, found 391.1195.
H-2,7), 7.65 (2H, m, o-Ph), 7.91 (1H, d, J = 15.6 Hz, COCHCH),
N-(4-Methoxycinnamoyl)-9-aminoanthracene 3k. Isolated as
8.04 (2H, d, J = 8.0 Hz, H-4,5), 8.09 (2H, d, J = 8.1 Hz, H-1,8), a yellow solid (95% yield); mp >310 °C; 1H NMR (600 MHz,
8.48 (1H, s, H-10); Rotamer B: δ 5.91 (1H, d, J = 15.5 Hz, DMSO-d6) δ 3.80 (3H, s), 7.01–7.07 (3H, m), 7.50–7.56 (4H, m),
COCH), 7.08 (2H, m, o-Ph), 7.14 (2H, m, m-Ph), 7.20 (1H, m, 7.59 (1H, d, J = 15.8 Hz), 7.67 (2H, d, J = 8.3 Hz), 8.02 (2H, d,
p-Ph), 7.53 (2H, m, H-3,6), 7.58 (2H, m, H-2,7), 7.86 (1H, d, J = J = 8.2 Hz), 8.13 (2H, m), 8.61 (1H, s), 10.50 (1H, s); 13C NMR
15.5 Hz, COCHCH), 8.10 (2H, d, J = 8.6 Hz, H-4,5), 8.22 (2H, d, (150.1 MHz, DMSO-d6) δ 55.3 (CH3), 114.5 (CH), 118.8 (CH),
J = 8.7 Hz, H-1,8), 8.58 (1H, s, H-10); 1H NMR (600 MHz, 123.8 (CH), 125.6 (CH), 125.9 (CH), 126.2 (CH), 127.2 (C), 127.9
DMSO-d6) 7.23 (1H, d, J = 15.9 Hz), 7.45 (1H, t, J = 7.5 Hz), 7.50 (C), 128.5 (CH), 129.4 (C), 129.6 (CH), 131.3 (C), 140.4 (CH),
(2H, t, J = 7.5 Hz), 7.53–7.59 (4H, m), 7.69 (1H, d, J = 15.9 Hz), 160.7 (C), 165.7 (C); FTIR (solid) ν = 3266, 1646, 1601, 1512,
7.73 (2H, d, J = 7.2 Hz), 8.08 (2H, m), 8.15 (2H, m), 8.63 (1H, s), 1254, 1176, 1036, 973, 830, 731 cm−1; MS [EI] m/z (%) 353 (M+,
10.55 (1H, s); 13C NMR (150.1 MHz, DMSO-d6) δ = 121.6 (CH), 64), 193 (96), 161 (91), 84 (100), 71 (88); HMRS (EI): m/z calcd
124.0 (CH), 125.6 (CH), 125.9 (CH), 126.1 (CH), 127.9 (CH), for C24H19NO2 [M+] 353.1416, found 353.1410.
127.9 (C), 128.5 (CH), 129.1 (CH), 129.5 (C), 129.9 (CH), 131.3
N-(3-Methylcinnamoyl)-9-aminoanthracene 3m. Isolated as
(C), 134.9 (C), 140.4 (CH), 165.2 (C); FTIR (solid) ν = 3253, a yellow solid (89% yield); mp >310 °C; 1H NMR (600 MHz,
1652, 1623, 1502, 1338, 1205, 963, 729, 695, 676 cm−1; MS (EI) DMSO-d6) δ 2.38 (s, 3H), 6.98 (1H, d, J = 6.9 Hz), 7.20–7.57 (7H,
m/z (%) 323 (M+, 69), 193 (100), 131 (31); HMRS (EI): m/z calcd m), 8.06 (2H, d, J = 8.9 Hz), 8.14 (2H, d, J = 7.0 Hz), 8.28 (1H, d,
for C23H17NO [M+] 323.1310, found 323.1306.
J = 8.8 Hz); 8.62 (1H, s), 10.51 (1H, s); 13C NMR (150.1 MHz,
N-(4-Methylcinnamoyl)-9-aminoanthracene 3e. Isolated as a DMSO-d6) δ 21.0 (CH3), 121.5 (CH) 124.0 (CH), 125.1 (CH),
yellow solid (82% yield); mp >310 °C; 1H NMR (600 MHz, 125.6 (CH), 125.9 (CH), 126.1 (CH), 127.9 (C), 128.4 (CH), 128.5
DMSO-d6) δ 2.36 (3H, s), 7.15 (1H, d, J = 15.6 Hz), 7.29 (2H, d, (CH), 129.0 (CH), 129.5 (C); 129.9 (C); 130.6 (CH), 131.3 (C);
J = 7.8 Hz), 7.52–7.57 (4H, m), 7.60 (2H, d, J = 8.4 Hz), 7.63 134.8 (C); 138.3 (C); 140.4 (CH), 165.2 (C); FTIR (solid) ν =
(1H, d, J = 15.6 Hz), 8.03–8.06 (2H, m), 8.12–8.15 (2H, m), 8.61 3250, 1650, 1614, 1504, 1018, 972, 952, 758, 729 cm−1; MS (EI)
(1H, s), 10.49 (1H, s); 13C NMR (150.1 MHz, DMSO-d6) δ 21.1 m/z (%) 337 (M+, 17), 193 (58), 145 (32), 86 (62), 84 (100%);
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HMRS (EI): m/z calcd for C24H19NO [M+], 337.1467, found (%) 413 (M+, 3,), 322 (22), 220 (100), 131 (34), 91 (54); HMRS
337.1471.
(EI): m/z calcd for C30H23NO [M+] 413.1779, found 413.1761.
N-Benzyl-N-(4-methylcinnamoyl)-9-aminoanthracene
3f.
Product isolated from the SiO2 column by elution with DCM as
a pale yellow solid (87% yield); mp 222–223 °C; 1H NMR
(600 MHz, CDCl3) δ 2.18 (3H, s), 5.19 (2H, s), 5.75 (1H, d, J =
General procedure for the synthesis of N-alkyl-N-cinnamoyl-9-
aminoanthracenes
The appropriate N-cinnamoyl-9-aminoanthracene (5.0 mmol), 15.6 Hz), 6.88 (4H, s), 7.06–7.12 (4H, m), 7.13–7.17 (1H, m),
alkyl iodide or benzyl bromide (0.60 mL, 5.0 mmol) and KButO 7.33 (2H, t, J = 7.5 Hz), 7.45 (2H, t, J = 7.2 Hz), 7.66 (2H, d, J =
(0.55 g, 5.0 mmol) in THF (100 mL) were stirred and heated 8.4 Hz), 7.77 (1H, d, J = 15.6 Hz), 8.05 (2H, d, J = 8.4 Hz), 8.53
under reflux for 2 h. On cooling, the THF was removed by (1H, s); 13C NMR (150.9 MHz, CDCl3) δ = 21.4 (CH3), 53.9
rotary evaporation and the residue partitioned between H2O (CH2), 117.3 (CH), 123.6 (CH), 125.8 (CH), 127.0 (CH), 127.7
(50 mL) and EtOAc (100 mL). The EtOAc was separated, (CH), 127.9 (CH), 128.0 (CH), 128.2 (CH), 128.6 (CH), 129.2
washed with brine (50 mL) and dried (MgSO4). Removal of the (CH), 129.5 (C), 130.5 (CH), 131.9 (C), 132.3 (C), 133.3 (C),
solvent gave the crude product, which was purified by column 137.2 (C), 139.9 (C), 143.2 (CH), 167.8 (C); FTIR (solid) ν =
chromatography on SiO2, the product eluting with 1 : 1 DCM– 1648, 1614, 1604, 1381, 1331, 1221, 1207, 815, 740, 700 cm−1
;
petrol to DCM depending upon the polarity of the product.
MS [EI] m/z (%) 427 (M+, 37), 283 (32), 234 (100), 145 (76), 91
N-Methyl-N-cinnamoyl-9-aminoanthracene 3b. Product iso- (58); HMRS (EI): m/z calcd for C24H19NO [M+] 427.1936, found
lated from the SiO2 column by elution with DCM + 5% Et2O as 427.1930.
a yellow solid (83% yield); mp 56–58 °C; 1H NMR (500 MHz,
N-Benzyl-N-(4-chlorocinnamoyl)-9-aminoanthracene
3h.
CDCl3) δ 3.58 (3H, s), 5.87 (1H, d, J = 15.5 Hz), 7.00 (2H, d, J = Product isolated from the SiO2 column by elution with 3 : 1
7.8 Hz), 7.09 (2H, t, J = 7.3 Hz), 7.11–7.15 (1H, m), 7.50–7.59 DCM–petrol as a pale yellow solid (82% yield); mp 210–211 °C;
(4H, m), 7.76 (1H, d, J = 15.5 Hz), 7.97 (2H, d, J = 8.7 Hz), 8.10 1H NMR (500 MHz, CDCl3) δ 5.18 (2H, s), 5.77 (1H, d, J = 15.5
(2H, d, J = 8.3 Hz), 8.56 (1H, s); 13C NMR (125.8 MHz, CDCl3) δ Hz), 6.88 (2H, d, J = 8.6 Hz), 7.13–7.16 (3H, m), 7.16–7.19 (1H,
37.0 (CH3), 118.1 (CH), 122.9 (CH), 126.0 (CH), 127.6 (CH), m), 7.31–7.38 (2H, m), 7.42–7.49 (2H, m), 7.64 (2H, d, J =
127.9 (CH), 128.5 (CH), 128.9 (CH), 128.9 (C), 129.5 (CH), 132.0 8.8 Hz), 7.73 (1H, d, J = 15.5 Hz), 8.05 (2H, d, J = 8.3 Hz), 8.70
(C), 134.5 (C), 135.0 (C), 142.7 (CH), 167.8 (C); FTIR (solid) ν = (1H, s); 13C NMR (125.8 MHz, CDCl3) δ = 54.0 (CH2), 118.9
1650, 1611, 1373, 1351, 1213, 1084, 762, 735 cm−1; MS (EI) m/z (CH), 123.4 (CH), 125.8 (CH), 127.1 (CH), 127.7 (CH), 128.1
(%) 337 (M+, 20), 207 (38), 144 (100), 131 (41); HMRS (EI): m/z (CH), 128.2 (CH), 128.6 (CH), 128.7 (CH), 129.0 (CH), 129.4 (C),
calcd for C24H19NO [M+] 337.1467, found 337.1456.
130.4 (CH), 131.9 (C), 133.0 (C), 133.5 (C), 135.3 (C), 137.0 (C),
N-Ethyl-N-cinnamoyl-9-aminoanthracene 3c. Product iso- 141.7 (CH), 167.2 (C); FTIR (solid) ν = 1648, 1614, 1381, 1213,
lated from the SiO2 column by elution with DCM + 5% Et2O as 984, 822, 739, 701 cm−1; MS [EI] m/z (%) 447 (M+, 12), 356 (12),
1
a grey solid (78% yield); mp 141–142 °C; H NMR (500 MHz, 283 (15), 254 (50), 91 (100); HMRS (EI): m/z calcd for
CDCl3) δ 1.21 (3H, t, J = 7.2 Hz), 4.12 (2H, q, J = 7.2 Hz), 5.83 C30H22ClNO [M+] 447.1390, found 447.1391.
(1H, d, J = 15.5 Hz), 6.98 (2H, d, J = 7.8 Hz), 7.08 (2H, t, J = 7.3
N-Benzyl-N-(4-trifluoromethylcinnamoyl)-9-aminoanthracene
Hz), 7.10–7.15 (1H, m), 7.50–7.57 (4H, m), 7.76 (1H, d, J = 15.5 3j. Product isolated from the SiO2 column by elution with 3 : 1
Hz), 7.97 (2H, d, J = 8.7 Hz), 8.10–8.13 (1H, m), 8.07–8.11 (1H, DCM–petrol as a white solid (73% yield); mp 164–165 °C;
m), 8.56 (1H, s); 13C NMR (125.8 MHz, CDCl3) δ 13.8 (CH3), 1H NMR (500 MHz, CDCl3) δ 5.20 (2H, s), 5.88 (1H, d, J =
45.5 (CH2), 118.6 (CH), 123.5 (CH), 125.9 (CH), 127.4 (CH), 15.5 Hz), 6.98–7.21 (6H, m), 7.30–7.42 (4H, m), 7.45 (2H, t, J =
127.8 (CH), 127.9 (CH), 128.5 (CH), 128.8 (CH), 129.4 (CH), 7.6 Hz), 7.65 (2H, d, J = 8.8 Hz), 7.80 (1H, d, J = 15.5 Hz), 8.06
129.7 (C), 132.0 (C), 133.4 (C), 135.1 (C), 142.6 (CH), 167.4 (C); (2H, d, J = 8.5 Hz), 8.56 (1H, s); 13C NMR (125.8 MHz, CDCl3)
FTIR (solid) ν = 1649, 1613, 1393, 1341, 1241, 977, 886, 845, δ 54.0 (CH2), 120.9 (CH), 123.3 (CH), 123.8 (C, q, J = 270 Hz),
764, 740 cm−1; MS (EI) m/z (%) 351 (M+, 11), 158 (100), 131 125.4 (CH, q, J = 3.8 Hz), 125.8 (CH), 127.2 (CH), 127.8 (CH),
(31), 84 (43; HMRS (EI): m/z calcd for C25H21NO [M+] 351.1623, 127.9 (CH), 128.2 (CH), 128.7 (CH), 129.4 (CH), 130.4 (CH),
found 351.1618.
131.0 (C, q, J = 32 Hz), 131.9 (C), 132.8 (C), 136.8 (C), 138.4 (C),
N-Benzyl-N-cinnamoyl-9-aminoanthracene 3d. Product iso- 141.3 (C), 141.4 (CH), 167.0 (C); FTIR (solid) ν = 1652, 1619,
lated from the SiO2 column by elution with DCM as a grey 1320, 1217, 1165, 1126, 1067, 833, 738, 702 cm−1; MS [EI] m/z
solid (75% yield); mp 138–140 °C; 1H NMR (600 MHz, CDCl3) δ (%) 481 (M+, 75), 390 (76), 288 (95), 193 (33), 91 (96%),
5.20 (2H, s), 5.82 (1H, d, J = 15.6 Hz), 6.98 (2H, d, J = 7.8 Hz), 84 (100); HMRS (EI): m/z calcd for C24H19NO [M+] 481.1654,
7.05–7.18 (8H, m), 7.34 (2H, dd, J = 7.8, 8.4 Hz), 7.46 (2H, t, J = found 481.1649.
7.2 Hz), 7.67 (2H, d, J = 8.4 Hz), 7.81 (1H, d, J = 15.6 Hz), 8.05
N-Benzyl-N-(4-methoxycinnamoyl)-9-aminoanthracene
3l.
(2H, d, J = 8.4 Hz), 8.55 (1H, s); 13C NMR (150.9 MHz, CDCl3) Product isolated from the SiO2 column by elution with DCM +
δ 54.0 (CH2), 118.3 (CH), 123.5 (CH), 125.8 (CH), 127.1 (CH), 5% Et2O as a white solid (86% yield); mp 202–203 °C; 1H NMR
127.7 (CH), 127.9 (CH), 128.1 (CH), 128.3 (CH), 128.5 (CH), (500 MHz, CDCl3) δ 3.66 (3H, s), 5.19 (2H, s), 5.68 (1H, d, J =
128.7 (CH), 129.5 (C), 129.6 (CH), 130.5 (CH), 131.9 (C), 133.2 15.4 Hz), 6.59 (2H, d, J = 8.7 Hz), 6.92 (2H, d, J = 8.7 Hz),
(C), 135.0 (C), 137.1 (C), 143.2 (CH), 167.6 (C); FTIR (solid) ν = 7.07–7.20 (4H, m), 7.31–7.35 (2H, m), 7.43–7.50 (2H, m), 7.66
1643, 1602, 1389, 1338, 1220, 997, 959, 740 cm−1; MS [EI] m/z (2H, d, J = 8.8 Hz), 7.75 (1H, d, J = 15.4 Hz), 8.04 (2H, d,
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J = 8.5 Hz), 8.53 (1H, s); 13C NMR (125.8 MHz, CDCl3) δ 53.9 (H-21, dt, J = 1.4, 7.4 Hz), 7.25 (H-15, dt, J = 1.3, 7.4 Hz), 7.29
(CH2), 55.3 (CH3), 113.9 (CH), 116.0 (CH), 123.6 (CH), 125.7 (H-16, dt, J = 1.4, 7.4 Hz), 7.36 (H-10, m), 7.37 (H-14, m), 7.46
(CH), 126.9 (CH), 127.6 (CH), 127.8 (C), 127.9 (CH), 128.2 (CH), (H-23, dd, J = 1.4, 7.2 Hz), 7.47 (H-20, dd, J = 1.4, 7.4 Hz), 7.51
128.6 (CH), 129.4 (CH), 129.5 (C), 130.4 (CH), 131.9 (C), 133.4 (H-17, dd, J = 1.4, 7.5 Hz); 13C NMR (125.8 MHz, CDCl3) δ 35.8
(C), 137.2 (C), 142.8 (C), 142.8 (CH), 160.8 (C), 167.8 (C); FTIR (C-13), 48.2 (C-5), 55.3 (C-12), 66.2 (C-1), 119.9 (C-17), 124.3
(solid) ν = 1647, 1616, 1594, 1509, 1257, 1214, 1167, 827, 738, (C-20), 125.0 (C-10), 126.8 (C-23), 127.0 (C-21), 127.4 (C-9),
698 cm−1; MS [EI] m/z (%) 443 (M+, 13), 283 (18), 250 (80), 161 127.4 (C-16), 127.6 (C-8), 127.7 (C-15), 127.8 (C-14), 128.2
(100), 91 (37); HMRS (EI): calcd for C24H19NO [M+] 443.1885, (C-22), 129.7 (C-7), 134.6 (C-6), 136.4 (C-13), 139.4 (C-11), 139.5
found 443.1878.
N-Benzyl-N-3-methyl-cinnamoyl-9-anthracene
(C-19), 141.8 (C-18), 144.5 (C-24), 178.0 (C-3); FTIR (solid) ν =
3n. Product 1696, 747, 722, 613, 477 cm−1; MS [EI] m/z (%) 323 (M+, 100),
isolated from the SiO2 column by elution with 3 : 1 DCM– 294 (20), 280 (41), 265 (27); HMRS (EI): m/z calcd for C23H17NO
petrol as a pale grey solid (90% yield); mp 127–128 °C; 1H [M+] 323.1310, found 323.1319.
NMR (600 MHz, CDCl3) δ 2.12 (3H, s), 5.19 (2H, s), 5.79 (1H, d,
(b) With TfOH. Following the general procedure, reaction of
J = 15.6 Hz), 6.76 (1H, d, J = 6.6 H), 6.80 (1H, s), 6.92–6.98 (2H, 3a (0.32 g) and purification as above gave the title product 4a
m), 7.06–7.12 (4H, m), 7.13–7.18 (1H, m), 7.34 (2H, dd, J = 6.6, (0.22 g, 69% yield).
7.8 Hz), 7.46 (2H, t, J = 7.5 Hz), 7.66 (2H, d, J = 8.4 Hz), 7.77
( )2-Methyl-2-azahexa-cyclo[10.6.6.01,5.06,11.013,18.019,24]tetra-
(1H, d, J = 15.6 Hz), 8.05 (2H, d, J = 8.4 Hz), 8.54 (1H, s); 13C cosa-6(11),7,9,13,15,17,19(24),20,22-nonaen-3-one 4b. Follow-
NMR (150.9 MHz, CDCl3) δ 21.2 (CH3), 54.0 (CH2), 118.1 (CH), ing the general procedure, reaction of 3b (0.34 g) with PPA and
123.6 (CH), 124.9 (CH), 125.8 (CH), 127.1 (CH), 127.7 (CH), elution of the SiO2 column with DCM + 5% Et2O gave the title
128.0 (CH), 128.2 (CH), 128.4 (CH), 128.7 (CH), 128.8 (CH), compound 4b (0.31 g, 89% yield) as a white solid; mp
129.5 (C), 130.4 (CH), 130.5 (CH), 131.9 (C), 133.2 (C), 134.9 240–242 °C; 1H NMR (500 MHz, CDCl3) δ 2.40 (1H, dd, J =
(C), 137.1 (C), 138.2 (C), 143.5 (CH), 167.7 (C); FTIR (solid) ν = 13.1, 15.7 Hz), 3.00 (1H, dd, J = 7.7, 15.7 Hz), 3.23 (3H, s), 3.57
1645, 1612, 1387, 1336, 1239, 961, 891, 849, 790, 740 702 cm−1
;
(1H, dd, J = 7.7, 13.1 Hz), 4.99 (1H, s), 6.86–6.89 (1H, m),
MS [EI] m/z (%) 427 (M+, 82), 336 (28), 283 (28), 234 (100), 145 7.00–7.02 (1H, m), 7.08–7.11 (2H, m), 7.20–7.23 (2H, m), 7.27
(21), 86 (35), 84 (57); HMRS (EI): calcd for C24H19NO [M+] (1H, dt, J = 1.4, 7.4 Hz), 7.29–7.34 (2H, m), 7.37–7.41 (2H, m),
427.1936, found 427.1930.
7.48 (1H, dd, J = 1.1, 7.3 Hz); 13C NMR (125.8 MHz, CDCl3) δ =
29.7 (CH3), 35.3 (CH2), 46.8 (CH), 55.2 (CH), 71.3 (C), 121.8
(CH), 125.1 (CH), 125.2 (CH), 126.7 (CH), 126.9 (CH), 127.3
General procedure for the PPA-mediated cyclisation
A
suspension of the N-cinnamoyl-9-aminoanthracene (CH), 127.3, (CH), 127.4 (CH), 127.6 (CH), 127.6 (CH), 128.2
(1.0 mmol) in CHCl3 (5 mL) and PPA (5 g) was heated to (CH), 129.8 (CH), 133.6 (C), 134.6 (C), 139.5 (C), 139.8 (C),
120 °C (block temperature), distilling off the CHCl3. After 141.1 (C), 144.7 (C), 176.4 (C); (solid) ν = 1691, 1367, 757, 747,
heating for 2 h, the reaction mixture was cooled and parti- cm−1; MS [EI] m/z (%) 337 (M+, 100), 265 (33); HMRS (EI): m/z
tioned between ice/water (50 g) and DCM (100 mL). The calcd for C24H19NO [M+] 337.1467, found 337.1471.
organic layer was separated, dried (MgSO4), filtered and con-
centrated in vacuo. The residue was purified by column 6(11),7,9,13,15,17,19(24),20,22-nonaen-3-one 4c. Following the
( )2-Ethyl-2-azahexacyclo[10.6.6.01,5.06,11.013,18.019,24]tetracosa-
chromatography on SiO2.
general procedure, 3c (0.36 g) was reacted with PPA and
elution of the SiO2 column with DCM + 5% Et2O gave the title
compound 4c (0.33 g, 90% yield) as a white solid; mp
General procedure for the TfOH-mediated cyclisation
Triflic acid (1 mL, 10 mmol) was added to a stirred solution of 204–205 °C; 1H NMR (500 MHz, CDCl3) δ 1.73 (3H, t, J =
the amide (2.0 mmol) in CHCl3 (20 mL) and the reaction 7.1 Hz), 2.36 (1H, dd, J = 12.8, 16.0 Hz), 3.00 (1H, dd, J = 7.8,
mixture was heated under gentle reflux until no starting 16.0 Hz), 3.09 (1H, dq, J = 7.1, 14.4 Hz), 3.57 (1H, dd, J = 7.8,
material was present by TLC. The reaction mixture was cooled 12.8 Hz), 3.93 (1H, dq, J = 7.1, 14.4 Hz), 4.93 (1H, s), 6.86–6.89
to room temperature, water (20 mL) was added and the (1H, m), 7.07–7.13 (3H, m), 7.18–7.22 (2H, m), 7.28 (1H, dt, J =
mixture basified with an excess of solid K2CO3 until CO2 1.2, 7.4 Hz), 7.30–7.35 (2H, m), 7.36–7.40 (1H, m), 7.48 (1H,
evolution ceased. The product was extracted into EtOAc dd, J = 1.2, 7.4 Hz), 7.56 (1H, dd, J = 0.8, 7.3 Hz); 13C NMR
(3 × 50 mL), dried (MgSO4), concentrated in vacuo and the (125.8 MHz, CDCl3) δ 14.6 (CH3), 35.9 (CH2), 39.6 (CH2), 46.9
product purified by column chromatography on SiO2.
(CH), 55.2 (CH), 73.0 (C), 121.6 (CH), 125.1 (CH), 125.5 (CH),
2-Azahexacyclo[10.6.6.01,5.06,11.013,18.019,24]tetracosa- 126.7 (CH), 126.8 (CH), 127.3 (CH), 127.3 (CH), 127.4 (CH),
6(11),7,9,13,15,17,19(24),20,22-nonaen-3-one 4a. (a) With PPA. 127.5 (CH), 128.1 (CH), 129.9 (CH), 134.7 (C), 139.6 (C), 140.9
Following the general procedure, reaction of 3a (0.32 g) with (C), 144.3 (C), 177.4 (C); FTIR (solid) ν = 1682, 1393, 1346,
PPA and elution of the SiO2 column with DCM + 5% Et2O gave 1315, 753, 743, 732 cm−1; MS [EI] m/z (%) 351 (M+, 100), 265
the title compound 4a (0.25 g, 78% yield) as a buff solid; mp (34); m/z calcd for C25H21NO [M+] 351.1623, found 351.1619.
234–236 °C; 1H NMR (500 MHz, CDCl3) δ 2.44 (H-4, dd, J =
( )2-Benzyl-2-azahexacyclo[10.6.6.01,5.06,11.013,18.019,24]tetra-
12.9, 16.0 Hz), 2.95 (H-4, dd, J = 7.6, 16.0 Hz), 3.75 (H-5, dd, J = cosa-6(11),7,9,13,15,17,19(24),20,22-nonaen-3-one 4d. Follow-
7.6, 12.9 Hz), 4.94 (H-12, s), 6.88 (H-7, m), 6.88 (NH, brs), 7.11 ing the general procedure, 3d (0.41 g) was reacted with PPA
(H-8, m), 7.13 (H-9, m), 7.21 (H-22, dt, J = 1.4, 2.3 Hz); 7.24 and elution of the SiO2 column with 2 : 1 DCM–petroleum
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ether gave the title compound 4d (0.36 g, 88% yield) as a white 4-phenyl-3,4-dihydro-1H-1-azacyclohept[de]anthracen-2-one 7.
1
solid; mp 230–231 °C; H NMR (600 MHz, CDCl3) δ 2.46 (1H, Following the general procedure, 3g (0.36 g) was reacted with
dd, J = 13.2, 16.2 Hz), 3.16 (1H, dd, J = 7.8, 16.2 Hz), 3.71 (1H, PPA and elution of the SiO2 column with 2 : 1 DCM–petroleum
dd, J = 7.8, 13.2 Hz), 4.06 (1H, d, J = 16.2 Hz), 4.94 (1H, s), 5.39 ether gave the title compound 7 (0.06 g, 16% yield) as an
(1H, d, J = 16.2 Hz), 6.90–6.95 (2H, m), 7.07 (1H, d, J = 7.8 Hz), orange solid; mp >310 °C; 1H NMR (600 MHz, CDCl3)
7.09–7.17 (4H, m), 7.23–7.28 (2H, m), 7.32–7.37 (2H, m), δ 3.31–3.41 (2H, m), 4.91–4.95 (1H, m), 7.06 (2H, d, J = 8.4 Hz),
7.40–7.45 (4H, m), 7.48 (2H, d, J = 7.2 Hz); 13C NMR 7.22 (2H, d, J = 8.4 Hz), 7.25–7.30 (1H, m), 7.39 (1H, t, J =
(150.1 MHz, CDCl3) δ 34.3 (CH2), 46.7 (CH), 48.1 (CH2), 55.2 7.8 Hz), 7.53–7.59 (2H, m), 7.99 (1H, d, J = 8.4 Hz), 8.03 (2H, d,
(CH), 73.7 (C), 122.8 (CH), 125.4 (CH), 125.5 (CH), 126.4 (CH), J = 8.8 Hz), 8.10 (1H, d, J = 8.8 Hz), 8.36 (1H, s); 13C NMR
127.0 (CH), 127.1 (CH), 127.3 (CH), 127.4 (CH), 127.6 (CH), (150.9 MHz, CDCl3) δ 41.7 (CH2), 47.7 (CH), 121.3 (CH), 122.4
127.7 (CH), 127.7 (CH), 128.3 (CH), 128.8 (CH), 130.0 (CH), (C), 123.8 (C), 124.9 (CH), 125.7 (CH), 126.2 (CH), 127.2 (CH),
134.6 (C), 134.7 (C), 138.5 (C), 139.6 (C), 139.7 (C), 140.3 (C), 128.2 (C), 128.7 (CH), 128.9 (CH), 129.2 (CH), 129.5 (CH), 129.7
144.7 (C), 177.9 (C); FTIR (solid) ν = 1689, 1357, 754, 745, (CH), 131.6 (C), 132.7 (C), 133.4 (C), 172.6 (C); MS [EI] m/z (%)
712 cm−1; MS [EI] m/z (%) 413 (M+, 100), 322 (19), 280 (45), 265 359 (M+, 35), 357 (M+, 100), 314 (85), 204 (23), 111 (24); m/z
(55), 91 (42); m/z calcd for C30H23NO [M+] 413.1779, found calcd for C23H16ClNO [M+] 357.0924, found 357.0925. Further
413.1780.
elution with DCM gave the title compound 4g (0.13 g, 36%
( )9-Methyl-2-azahexacyclo[10.6.6.01,5.06,11.013,18.019,24]tetracosa- yield) as a light brown solid; mp >310 °C; H NMR (500 MHz,
6(11),7,9,13,15,17,19(24),20,22-nonaen-3-one 4e. Following the CDCl3) δ 2.40 (1H, dd, J = 12.9, 14.5 Hz), 2.91 (1H, dd, J = 7.6,
general procedure, 3e (0.34 g) was reacted with PPA and 14.5 Hz), 3.68 (1H, dd, J = 7.6, 12.9 Hz), 4.89 (1H, s), 6.75–6.82
elution of the SiO2 column with DCM gave the title compound (2H, m), 7.08 (1H, dm, J = 6.4 Hz), 7.2–7.34 (4H, m), 7.35–7.39
1
4e (0.28 g, 82% yield) as a light brown solid; mp >310 °C; H (2H, m), 7.42–7.53 (3H, m); 13C NMR (125.8 MHz, CDCl3) δ
1
NMR (500 MHz, CDCl3) δ 2.29 (3H, s), 2.41 (1H, dd, J = 12.9, 35.6 (CH2), 47.8 (CH), 54.9 (CH), 65.9 (C), 119.9 (CH), 124.3
16.0 Hz), 2.92 (1H, dd, J = 7.6, 16.0 Hz), 3.70 (1H, dd, J = 7.6, (CH), 125.1 (CH), 126.8 (CH), 127.3 (CH), 127.6 (CH), 127.7
12.9 Hz), 4.88 (1H, s), 6.68 (1H, s), 6.76 (1H, d, J = 7.8 Hz), 6.92 (CH), 127.7 (CH), 128.3 (CH), 131.1 (CH), 132.7 (C), 133.0 (C),
(1H, d, J = 7.8 Hz), 7.16–7.29 (5H, m), 7.37 (1H, dd, J = 1.4, 7.5 136.2 (C), 138.8 (C), 140.9 (C), 141.6 (C), 143.8 (C), 177.1 (C);
Hz), 7.42–7.46 (2H, m), 7.49 (1H, d, J = 7.4 Hz); 13C NMR FTIR (solid) ν = 1702, 1346, 841, 815, 759, 748, 722 cm−1; MS
(125.8 MHz, CDCl3) δ 21.0 (CH3), 35.8 (CH2), 47.9 (CH), 55.3 [EI] m/z (%) 359 (M+, 35), 357 (M+, 100), 314 (34), 299 (14), 279
(CH), 66.2 (C), 119.8 (CH), 124.2 (CH), 124.9 (CH), 126.6 (CH), (13), 165 (20), 84 (25); m/z calcd for C23H16ClNO [M+] 357.0924,
126.9 (CH), 127.3 (CH), 127.5 (CH), 128.1 (CH), 128.2 (CH), found 357.0926.
128.5 (CH), 129.5 (CH), 131.4 (C), 136.4 (C), 137.1 (C), 139.0
( )2-Benzyl-9-chloro-2-azahexacyclo[10.6.6.01,5.06,11.013,18.019,24]-
(C), 141.8 (C), 144.6 (C), 177.6 (C); FTIR (solid) ν = 1694, 1346, tetracosa-6(11),7,9,13,15,17,19(24),20,22-nonaen-3-one 4h. Fol-
818, 763, 731, cm−1; MS [EI] m/z (%) 337 (M+, 100), 294 (28), lowing the general procedure, 3h (0.45 g) was reacted with PPA
279 (22), 86 (29), 84 (47); m/z calcd for C24H19NO [M+] and elution of the SiO2 column with DCM gave the title com-
337.1467, found 337.1467.
pound 4h (0.2 g, 45% yield) as a white solid; mp 308–309 °C;
( )2-Benzyl-9-methyl-2-azahexacyclo[10.6.6.01,5.06,11.013,18.019,24]- 1H NMR (600 MHz, CDCl3) δ 2.41 (1H, dd, J = 13.2, 16.2 Hz),
tetracosa-6(11),7,9,13,15,17,19(24),20,22-nonaen-3-one 4f. Follow- 3.12 (1H, dd, J = 7.8, 16.2 Hz), 3.64 (1H, dd, J = 7.8, 13.2 Hz),
ing the general procedure, 3f (0.43 g) was reacted with PPA and 4.03 (1H, d, J = 15.6 Hz), 4.89 (1H, s), 5.37 (1H, d, J = 15.6 Hz),
elution of the SiO2 column with DCM gave the title compound 6.85 (1H, d, J = 8.4 Hz), 6.93 (1H, dt, J = 0.6, 7.5 Hz), 7.06 (1H,
4f as a white solid (0.38 g, 88% yield); mp 288–289 °C; 1H d, J = 7.8 Hz), 7.09 (1H, dd, J = 2.4, 8.4 Hz), 7.12–7.15 (1H, m),
NMR (600 MHz, CDCl3) δ 2.28 (3H, s), 2.42 (1H, dd J = 12.6, 7.17 (1H, dt, J = 0.6, 7.5 Hz), 7.26–7.30 (2H, m), 7.32–7.36 (2H,
16.2 Hz), 3.13 (1H, dd, J = 7.8, 16.2 Hz), 3.66 (1H, dd, J = 7.8, m), 7.39–7.47 (6H, m); 13C NMR (150.9 MHz, CDCl3) δ 35.7
12.6 Hz), 4.04 (1H, d, J = 15.6 Hz), 4.89 (1H, s), 5.37 (1H, d, J = (CH2), 46.3 (CH), 48.1 (CH2), 54.8 (CH), 73.5 (C), 122.9 (CH),
15.6 Hz), 6.91 (1H, d, J = 7.8 Hz), 6.89–6.94 (2H, m), 7.06 (1H, 126.5 (CH), 127.3 (CH), 127.3 (CH), 127.4 (CH), 127.5 (CH),
d, J = 7.2 Hz), 7.12–7.17 (3H, m), 7.23–7.27 (2H, m), 7.34 (1H, t, 127.5 (CH), 127.6 (CH), 127.7 (CH), 128.4 (CH), 128.8 (CH),
J = 7.2 Hz), 7.39–7.43 (4H, m), 7.46 (2H, d, J = 7.2 Hz); 13C 131.5 (CH), 132.6 (C), 133.1 (C), 134.4 (C), 138.4 (C), 140.1 (C),
NMR (150.9 MHz, CDCl3) δ 21.1 (CH3), 35.8 (CH2), 46.4 (CH), 141.2 (C), 143.9 (C), 177.6 (C); FTIR (solid) ν = 1693, 1475,
48.1 (CH2), 55.3 (CH), 73.7 (C), 122.8 (CH), 125.3 (CH), 125.5 1394, 1356, 852, 812, 751, 716 cm−1; MS [EI] m/z (%) 449 (M+,
(CH), 126.3 (CH), 127.0 (CH), 127.1 (CH), 127.2 (CH), 127.4 35), 447 (M+, 100), 356 (15), 314 (26), 299 (17), 279 (17); m/z
(CH), 127.7 (CH), 128.3 (CH), 128.3 (CH), 128.3 (CH), 128.8 calcd for C30H22ClNO [M+] 447.1390, found 447.1379.
(CH), 129.9 (CH), 131.5 (C), 134.6 (C), 137.1 (C), 138.6 (C),
( )9-Methoxy-2-azahexacyclo[10.6.6.01,5.06,11.013,18.019,24]tetra-
139.4 (C), 139.6 (C), 140.3 (C), 144.7 (C), 178.0 (C); FTIR (solid) cosa-6(11),7,9,13,15,17,19(24),20,22-nonaen-3-one 4k. Follow-
ν = 1688, 1392, 1353, 810, 762, 749, 735, 709 cm−1; MS [EI] m/z ing the general procedure, 3k (0.35 g) was reacted with PPA
(%) 427 (M+, 100), 336 (15), 294 (21), 279 (27); HMRS (EI): m/z and elution of the SiO2 column with DCM gave the title com-
calcd for C24H19NO [M+] 427.1936, found 427.1939.
pound 4k as a light grey solid (0.11 g, 31% yield); mp >310 °C;
( )9-Chloro-2-azahexacyclo[10.6.6.01,5.06,11.013,18.019,24]tetra- 1H NMR (600 MHz, CDCl3) δ 2.40 (1H, dd, J = 13.2, 16.2 Hz),
cosa-6(11),7,9,13,15,17,19(24),20,22-nonaen-3-one 4g and 2.91 (1H, dd, J = 7.8, 16.2 Hz), 3.67 (1H, dd, J = 7.8, 13.2 Hz),
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3.78 (3H, s), 6.65 (1H, dd, J = 3.0, 8.4 Hz), 6.75 (1H, brs), 6.79 pound 4n (0.37 g, 87% yield) as a pale yellow solid; mp
(1H, d, J = 8.4 Hz), 6.93 (1H, d, J = 3.0 Hz), 7.19–7.27 (3H, m), 156–158 °C; 1H NMR (600 MHz, CDCl3) δ 2.23 (3H, s), 2.49
7.29 (1H, t, J = 6.9 Hz), 7.36 (1H, d, J = 6.6 Hz), 7.45 (2H, m), (1H, dd, J = 12.6, 16.2 Hz), 3.18 (1H, dd, J = 7.8, 16.2 H), 3.70
7.50 (1H, d, J = 7.8 Hz); 13C NMR (150.9 MHz, CDCl3) δ 36.0 (1H, dd, J = 7.8, 12.6 Hz), 4.08 (1H, d, J = 16.2 Hz), 4.95 (1H, s),
(CH2), 47.7 (CH), 55.4 (CH), 55.4 (CH3), 66.2 (C), 112.2 (CH), 5.41 (1H, d, J = 16.2 Hz), 6.76 (1H, s), 6.90–6.97 (2H, m), 7.10
113.8 (CH), 119.9 (CH), 124.3 (CH), 125.0 (CH), 126.5 (C), 126.8 (1H, d, J = 7.2 Hz), 7.14–7.19 (2H, m), 7.24–7.30 (3H, m), 7.37
(CH), 127.0 (CH), 127.5 (CH), 127.6 (CH), 128.1 (CH), 130.8 (C), (1H, t, J = 7.2 Hz), 7.40–7.48 (4H, m), 7.50 (2H, d, J = 7.2 Hz);
136.5 (C), 139.2 (C), 140.4 (C), 141.8 (C), 144.2 (C), 158.5 (C), 13C NMR (150.9 MHz, CDCl3) δ 21.3 (CH3), 36.0 (CH2), 46.8
177.7 (C); FTIR (solid) ν = 1700, 1661, 1350, 1257, 981, 801, (CH), 48.3 (CH2), 54.7 (CH), 73.9 (C), 123.6 (CH), 126.3 (CH),
731 cm−1; MS [EI] m/z (%) 353 (M+, 100), 310 (16), 86 (20), 84 126.9 (CH), 127.1 (CH), 127.3 (CH), 127.4 (CH), 127.6 (CH),
(30); HMRS (EI): m/z calcd for C24H19NO2 [M+] 353.1416, found 127.8 (CH), 128.0 (CH), 128.3 (CH), 128.8 (CH), 130.9 (CH),
353.1419.
134.4 (C), 134.6 (C), 136.9 (C), 137.4 (C), 138.6 (C), 139.8 (C),
( )2-Benzyl-9-methoxy-2-azahexacyclo[10.6.6.01,5.06,11.013,18.019,24]- 140.3 (C), 145.0 (C), 178.2 (C); FTIR (solid) ν = 1698, 1454,
tetracosa-6(11),7,9,13,15,17,19(24),20,22-nonaen-3-one 4l. Follow- 1346, 1320, 744, 710 cm−1; MS [EI] m/z (%) 427 (M+, 100), 336
ing the general procedure, 3l (0.44 g) was reacted with TfOH, (20), 294 (23), 279 (24), 86 (58), 84 (89); m/z calcd for C31H25NO
but with stirring at room temperature for 1 h and elution of [M+] 427.1936, found 427.1931.
the SiO2 column with DCM gave the title compound 4l as a
N-(Anthracen-9-yl-ethyl)-3-phenylacryl-amide 8. To a stirred
white solid (0.34 g 77% yield); mp 268–269 °C; 1H NMR solution of LAH (5 mL of a 2 M solution) in dry THF (30 mL)
(600 MHz, CDCl3) δ 2.40 (1H, dd, J = 12.6, 16.2 Hz), 3.11 (1H, under Ar at −78 °C was added, in one portion, AlCl3 0.5 g,
dd, J = 7.8, 16.2 Hz), 3.63 (1H, dd, J = 7.8, 12.6 Hz), 3.77 (3H, 3.7 mmol) and the solution warmed to 0 °C over 10 min. On
s), 4.04 (1H, d, J = 15.6 Hz), 4.87 (1H, s), 5.37 (1H, d, J = 15.6 re-cooling to −78 °C, 9-(2-nitrovinyl)anthracene (1.3 g,
Hz), 6.65 (1H, dd, J = 3.0, 8.4 Hz), 6.83 (1H, d, J = 8.4 Hz), 6.89 5.2 mmol)11 was added in one portion and the reaction
(1H, d, J = 3.0 Hz), 6.91 (1H, dt, J = 1.2, 7.8 Hz), 7.06 (1H, d, J = mixture allowed to warm to room temperature, then heated to
7.2 Hz), 7.11–7.17 (2H, m), 7.23–7.27 (2H, m), 7.34 (1H, t, J = 40 °C for 30 min. On cooling to 0 °C, 50 mL of THF was
7.2 Hz), 7.39–7.44 (4H, m), 7.46 (2H, d, J = 7.2 Hz); 13C NMR added, followed by careful addition of 2 M NaOH (3 mL). After
(150.9 MHz, CDCl3) δ 36.0 (CH2), 46.2 (CH), 48.1 (CH2), 55.4 stirring for 30 min, Et3N (0.7 mL, 5 mmol) and cinnamoyl
(CH), 55.4 (CH3), 73.8 (C), 112.3 (CH), 113.6 (CH), 122.8 (CH), chloride (0.8 g 4.8 mmol) were added, and the reaction stirred
125.4 (CH), 125.5 (CH), 126.4 (CH), 126.5 (C), 127.0 (CH), 127.2 at room temperature for 1 h. The reaction mixture was filtered
(CH), 127.2 (CH), 127.4 (CH), 127.7 (CH), 128.3 (CH), 131.1 through celite and the collected solids washed with DCM
(CH), 134.6 (C), 138.5 (C), 139.2 (C), 140.3 (C), 140.7 (C), 144.3 (3 × 50 mL). The combined organics were concentrated by
(C), 158.4 (C), 178.0 (C); FTIR (solid) ν = 1688, 1501, 1351, rotary evaporation and the residue re-dissolved in 9 : 1 Et2O–
1244, 1034, 842, 762, 732, 712 cm−1; MS [EI] m/z (%) 443 (M+, DCM. This solution was then washed with 2 M HCl (30 mL),
100), 352 (15), 310 (21), 295 (16), 91 (21); HMRS (EI): calcd for H2O (3 × 30 mL) and 1 M NaOH (30 mL) and dried (MgSO4),
C24H19NO [M+] 443.1885, found 443.1890.
( )8-Methyl-2-azahexacyclo[10.6.6.01,5.06,11.013,18.019,24]tetra- gave an oil which, on trituration with ether gave the title com-
cosa-6(11),7,9,13,15,17,19(24),20,22-nonaen-3-one 4m. Fol- pound (0.8 g) as pale yellow solid. Purification of the concen-
Filtration and removal of the solvent by rotary evaporation
lowing the general procedure, 3m (0.34 g) was reacted with trated mother liquors by column chromatography on SiO2,
PPA and elution of the SiO2 column with DCM gave the title eluting with 3 : 1 DCM/petrol–DCM gave a further 0.45 g of
compound 4m (0.25 g, 73% yield) as a light brown solid; mp product, total yield 1.25 g, (68% yield); mp 189–190 °C; 1H
304–306 °C; 1H NMR (500 MHz, CDCl3) δ 2.20 (3H, s), 2.44 NMR (600 MHz, CDCl3) δ 3.83 (2H, m), 3.96 (2H, 7.3 Hz), 5.79
(1H, dd, J = 12.9, 16.0 Hz), 2.94 (1H, dd, J = 7.6, 16.0 Hz), 3.71 (1H, brs), 6.25 (1H, d, J = 15.6 Hz), 7.25 (1H, s), 7.32–7.38 (2H,
(1H, dd, J = 7.6, 12.9 Hz), 4.91 (1H, s), 6.69 (1H, s), 6.95 (1H, d, m), 7.43–7.49 (3H, m), 7.53 (2H, ddd, J = 1.2, 6.4, 7.7 Hz),
J = 7.6 Hz), 7.17–7.30 (6H, m), 7.35 (1H, d, J = 7.1 Hz), 7.44 7.62 (1H, d, J = 15.6 Hz), 8.02 (2H, d, J = 8.4 Hz), 3.70 (2H, d, J
(1H, d, J = 7.2 Hz), 7.45–7.50 (2H, m), 7.53 (1H, d, J = 7.4 Hz); = 8.9 Hz), 8.39 (1H, s); 13C NMR (150.9 MHz, CDCl3) δ 27.8
13C NMR (125.8 MHz, CDCl3) δ 21.0 (CH3), 35.9 (CH2), 48.2 (CH2), 40.9 (CH2), 120.6 (CH), 124.4 (CH), 125.2 (CH), 126.2
(CH), 55.0 (CH), 66.4 (C), 119.9 (CH), 124.3 (CH), 124.8 (CH), (CH), 126.7 (CH), 127.9 (CH), 128.9 (CH), 129.3 (CH), 129.8
126.6 (CH), 126.8 (CH), 127.3 (CH), 127.5 (CH), 127.6 (CH), (CH), 130.3 (C), 131.0 (C), 131.7 (C), 134.9 (C), 141.2 (CH),
128.0 (CH), 128.1 (CH), 130.3 (CH), 134.3 (C), 136.5 (C), 136.5 166.5 (C); FTIR (solid) ν = 3302, 1651, 1613, 1535, 1329, 1215,
(C), 137.3 (C), 139.7 (C), 141.8 (C). 144.7 (C), 178.1 (C); FTIR 1120, 969, 873, 834, 727, 714, 658 cm−1; MS [EI] m/z (%) 351
(solid) ν = 3180, 1697, 1343, 812, 736 cm−1; MS [EI] m/z (%) (M+, 8), 204 (41), 191 (100), 189 (48), 131 (85), 103 (53), 69 (51);
337 (M+, 100), 294 (30), 279 (25), 86 (18), 84 (29); m/z calcd for m/z calcd for C25H21NO [M+] 351.1623, found 351.1620.
C24H19NO [M+] 337.1467, found 337.1452.
( )2-Benzyl-8-methyl-2-azahexacyclo[10.6.6.01,5.06,11.013,18.019,24]- 01,19.02,7.09,14]icosa-2,4,6,9(14),10,12-hexaen-18-one 9. Follow-
tetracosa-6(11),7,9,13,15,17,19(24),20,22-nonaen-3-one 4n. Fol- ing the general procedure for the PPA cyclisation, 9 (0.70 g,
(19S,20R)(19R,20S)-20-Phenyl-17-azapentacyclo[6.-6-.6.-
lowing the general procedure, 3n (0.43 g) was reacted with PPA 2 mmol) was heated for 30 min at 130 °C (heating block temp-
and elution of the SiO2 column with DCM gave the title com- erature). The product was purified by column chromatography
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on SiO2, eluting with 5% EtOAc–DCM, isolated as a cream 123.2 (CH), 126.1 (CH), 126.2 (CH), 126.3 (CH), 126.6 (CH),
solid from ether trituration (0.67 g, 96% yield); mp 126.8 (CH), 127.1 (CH), 127.7 (CH), 128.5 (CH), 138.4 (C), 140.8
159–160 °C; 1H NMR (600 MHz, CDCl3) δ 2.77 (3H, s), 5.80 (C), 143.6 (C), 143.8 (C), 146.7 (C), 173.6 (C); FTIR (solid) ν =
(2H, s), 6.88 (1H, d, J = 15.6 Hz), 7.32–7.40 (3H, m), 7.50 (2H, t, 1686, 1398, 776, 765, 755, 731, 704, 591 cm−1; MS [EI] m/z (%)
J = 7.5 Hz), 7.52–7.59 (4H, m), 7.86 (1H, d, J = 15.6 Hz), 8.05 351 (M+, 100), 220 (58), 191 (49); m/z calcd for C25H21NO [M+]
(2H, d, J = 8.4 Hz), 8.37 (2H, d, J = 8.4 Hz), 8.50 (1H, s); 351.1623, found 351.1620.
13C NMR (150.9 MHz, CDCl3) δ 33.2 (CH3), 41.9 (CH2), 117.8
(CH), 124.3 (CH), 125.3 (CH), 126.9 (CH), 127.8 (C), 128.0 (CH),
128.5 (CH), 128.9 (CH), 129.4 (CH), 129.8 (CH), 131.5 (C), 135.4
(C), 143.2 (C), 143.2 (CH), 166.7 (C); FTIR (solid) ν = 1647,
Acknowledgements
1593, 1408, 1242, 1115, 990, 885, 760, 733, 701, 518 cm−1; MS The authors would like to thank Vincent Gray for the mass
[EI] m/z (%) 351 (M+, 64), 204 (100), 191 (83), 189 (29), 131 (47), spectra and Karen Joiner for assistance with nomenclature.
103 (19); m/z calcd for C25H21NO [M+] 351.1623, found
351.1627.
N-(Anthracen-9-yl-methyl)-N-methyl-3-phenylacryl-amide 10.
To a stirred solution of N-anthracen-9-yl-methyl-methylamine
References
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was added cinnamoyl chloride (0.77 g, 4.6 mmol) in DCM
(20 mL) and stirred at room temperature for 1 h. Water
(20 mL) was added and the solid collected, washed with water
(20 mL), Et2O (2 × 50 mL) and dried (1.5 g, 92% yield). A small
sample was recrystallised from EtOAc–petroleum ether as a
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white solid, mp 211–212 °C; H NMR (600 MHz, CDCl3) δ 2.77
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(3H, s), 5.80 (2H, s), 6.88 (1H, d, J = 15.6 Hz), 7.32–7.40 (3H,
m), 7.50 (2H, t, J = 7.5 Hz), 7.52–7.59 (4H, m), 7.86 (1H, d, J =
15.6 Hz), 8.05 (2H, d, J = 8.4 Hz), 8.37 (2H, d, J = 8.4 Hz), 8.50
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117.8 (CH), 124.3 (CH), 125.3 (CH), 126.9 (CH), 127.8 (C), 128.0
(CH), 128.5 (CH), 128.9 (CH), 129.4 (CH), 129.8 (CH), 131.5 (C),
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