A simple route to benz[a]acridinium salts

Article abstract of DOI:10.1515/znb-2011-0711

By reaction of N-substituted N-phenyl-2-naphthylamimes with the Vilsmeier reagent N-substituted benz[a]acridinium salts are formed in satisfactory yields. 2011 Verlag der Zeitschrift fuer Naturforschung, Tuebingen.

Full text of DOI:10.1515/znb-2011-0711

A Simple Route to Benz[a]acridinium Salts
Horst Hartmann
Department Chemie, Technische Universita¨t Dresden, 01062 Dresden, Germany
Reprint requests to Prof. Dr. Horst Hartmann. Fax: ++49-351-4633 9485. E-mail: Hartmann@iapp.de
Z. Naturforsch. 2011, 66b, 711 – 714; received May 5, 2011
Dedicated to Prof. Dr. Dr. hc mult. Siegfried Hu¨nig to the occasion of his 90th birthday
By reaction of N-substituted N-phenyl-2-naphthylamimes with the Vilsmeier reagent N-substituted
benz[a]acridinium salts are formed in satisfactory yields.
Key words: Vilsmeier Reaction, N-Substituted 2-(N-Phenyl)-naphthylamines, Benz[a]acridinium
Perchlorates
Introduction
aldehydes 5, the 1,3,3,4-tetrahydro-3-quinazolinium
salts 6 were obtained [3]. These compounds arise
by cyclisation of the corresponding dimethyliminium
salts 4 intermediately formed in the course of the VR
and can be regarded as undesired by-products in the
Vilsmeier aldehyde synthesis (Scheme 1). In contrast,
the mono-formyl compounds 2 and the bis-formyl
derivatives 3 are important starting materials for a va-
riety of products with some practical interest, such as
organic dyes with intense absorption in the visible or
near infrared region [4], with highly non-linear opti-
cal properties [5], or with a high two-photon cross sec-
tion [6].
As has been known for a long time, the Vilsmeier
reaction (VR), usually performed with a mixture of
DMF and POCl3, is a versatile method for prepar-
ing aromatic or heteroaromatic aldehydes in an enor-
mous variety [1]. For instance, by starting with 4-
unsubstituted N,N-dialkylanilines 1a, N,N-disubstitut-
ed 4-aminobenzaldehydes 2 or, under more rigor-
ous conditions, corresponding N,N-disubstituted 4-
amino-terephthalaldehydes3 are formed [2]. However,
by starting with 4-substituted N,N-dialkylanines 1b,
instead of expected N,N-disubstituted 2-amino-benz-
Scheme 1. VR = Vilsmeier reaction.
c
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712
H. Hartmann · A Simple Route to Benz[a]acridinium Salts
after addition of aqueous perchloric acid to the reaction
mixture and were obtained in rather high yields.
The necessary N-substituted N-phenyl-2-naphthyl-
amines 12 are commercially not available, but they
can be synthesised easily from the N−unsubstituted N-
phenyl-2-naphthylamine parent compound 11 by addi-
tion of an appropriate alkylating agent of the general
formula R-X before starting the Vilsmeier formyla-
tion. The N,N-diphenyl-2-naphthylamine 10g was pre-
pared, however, by a palladium-catalysed C-N cross
coupling from N-phenyl-2-naphthylamine and bromo-
benzene [12].
The benz[a]acridiniumsalts 15 so prepared are pale-
yellow solids. Their structures follow unambiguously
from the analytic data. For instance, all salts exhibit
in the mass spectra m/z values which are in accord
with the cationic moieties, and in the 1H NMR spectra
they show characteristic signals between δ = 7.8 – 9.5
and ∼ 10.0 ppm. Whereas the former signals originate
from the protons at the carbocyclic rings, the latter sig-
nals can be attributed to the protons at C12 of the hete-
rocyclic azine ring in the benzo[c]acridinium salts 15.
In contrast to acridines [13], acridinium salts are
hitherto sparsely known and usually prepared by alky-
lation of their non-ionic parent compounds [14]. Be-
cause they are of some interest for various applications,
e. g. as chemotherapeutics (e. g. Acriflavine), as fluo-
rescent stains [15], or as organic dyes [16], the sim-
ple access described will make further studies on these
compounds much easier.
Scheme 2.
The Vilsmeier formylation of N,N-dialkylanilines 1
outlined here starts similarly with N-monoaryl- and
N,N-diaryl-substituted aniline derivatives and gives
rise to the formation of corresponding N-mono-
aryl- and N,N-diaryl-substituted aldehydes or their
dimethyliminium salt precursors (Scheme 2). Thus,
N-methyl-diphenylamine 7a, triphenylamine 8a, N-
methyl-N-phenyl-1-naphthylamine 9a, and N,N-di-
phenyl-1-naphthylamine 10a were converted by a VR
into the corresponding N-methyl-N-phenyl-4-amino-
benzaldehyde 7b [7], N,N-diphenyl-4-aminobenzal-
dehyde 8b [8], N-methyl-N-phenyl-4-amino-1-naph-
thaldehyde 9b [9], and N,N-diphenyl-4-amino-1-naph-
thaldehyde 10b [10], respectively. Under more rig-
orous conditions the bis-formyl derivatives 7c – 10c
as well as the tris-formyl derivative 8d were formed
[8a, 11].
Results and Discussion
A quite different result has been found, however,
when N-phenyl-substituted 2-naphthylamines 12 were
used as reactants in the VR. Instead of the corre-
sponding formyl compounds 14 (or their correspond-
ing dimethyliminium salt precursors 13) benz[a]acrid-
inium salts of the general structure 15 were obtained
(Scheme 3).
The reaction can be advantageously performed by
heating a mixture of the Vilsmeier reagent with the ap-
propriate N-phenyl-substituted 2-naphthylamine 12 at
80 – 90 ◦C for several hours and quenching the reaction
mixture after cooling by pouring into methanol. The
benz[a]acridinium salts 15 so formed could be isolated Scheme 3.
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H. Hartmann · A Simple Route to Benz[a]acridinium Salts
713
Experimental Section
δ = 1.80 (t, 3H, CH3), 5.99 (q, 2H, CH2), 7.78 (t, 1H), 7.81 –
7.93 (m, 2H), 8.00 (d, J = 7.9 Hz, 1H), 8.15 (d, J = 9.7 Hz,
1H), 8.26 (t, 1H), 8.37 (d, J = 9.2 Hz, 1H), 8.44 (d, J = 8.2 Hz,
1H), 8.53 (d, J = 9.8 Hz, 1H), 8.84 (d, J = 8.3 Hz, 1H),
10.19 (s, 1H). – MS (−(+)ESI): m/z = 258.1 (calcd. 258.34; for
C19H16N+, [M–ClO ]+). – C19H19ClNO4 (357.79): calcd.
C 63.78, H 4.51, Cl 49.91, N 3.91, O 17.89; found C 63.64,
H 4.81, N 4.55.
1H NMR spectra were recorded in trifluoroacetic acid
with a Bruker DRX 500 P instrument at 500.13 MHz.
The melting points were measured with a Boetius heating-
table microscope. Mass spectra were recorded with a Bruker
Esquire-LC 00084 instrument at 10 V with electrospray ion-
isation using methanol containing 0.1 % ammonium acetate.
7-Methoxycarbonylmethyl-benzo[a]acridinium perchlo-
rate (15c) in a yield of 75 %. M. p. 290 – 292 ◦C. – 1H NMR
(400 MHz, CF3COOH): δ = 4.47 (s, 3H, CH3), 6.71 (s, 2H,
H2), 8.39 (t, 1H), 8.49 – 8.61 (m, 4H), 8.74 – 8.85 (m, 2H),
9.03 (d, J = 11.2 Hz, 1H), 9.12 (d, J = 12.8 Hz, 1H), 9.43
(d, J = 11.2 Hz, 1H), 10.87 (s, 1H). – MS ((+)ESI−): m/z =
302.1 (calcd. 302.35 for C20H16NO2+, [M–ClO4 ]+). –
C20H16ClNO6 (401.80): calcd. C 59.78, H 4.01, Cl 8.82,
N 3.49, O 23.89; found C 59.24, H 4.01, N 3.45.
7-Benzyl-benzo[a]acridinium perchlorate (15d) in a yield
of 92 %. M. p. 288 – 289 ◦C. – 1H NMR (400 MHz,
CF3COOH): δ = 7.02 (s, 2H, CH2), 7.56 (d, J = 12.0 Hz,
2H), 7.80 (m, 2H), 8.36 (t, 1H), 8.47 – 8.61 (m, 3H), 8.72
(t, 1H), 8.20 (d, J = 12.0 Hz, 1H), 8.99 (t, 2H), 9.46
(d, J = 11.6 Hz, 1H), 10.88 (s, 1H). – MS ((−+)ESI):
m/z = 320.2 (calcd. 320.41 for C24H18N+, [M–ClO4 ]+). –
C24H18ClNO4 (419.86): calcd. C 68.66, H 4.32, Cl 8.44,
N 3.34; O 15.24; found C 69.04, H 4.31, N 3.54.
Preparation of N,N-diphenyl-2-naphthylamine (12g)
To a solution of N-phenyl-2-naphthylamine (11, 54.8 g,
0.25 mol), bromobenzene (39.3 g, 0.25 mol) and Na-tert.-
butanolate (28.8 g, 0.3 mol) in toluene (500 mL) a solution
of palladium-bis-(tri-tert.-butylphosphane) (10 mL, 10 %) in
toluene was added dropwise under argon at r. t. After reflux-
ing the resulting mixture for 8 h, it was cooled to r. t. and
mixed with water (500 mL). The organic phase was sepa-
rated and the aqueous solution extracted twice with diethyl
ether (250 mL). The organic solutions were combined, dried
with MgSO4, and evaporated in vacuo. The product so ob-
tained in a yield of 74 g was purified by recrystallisation from
a toluene/cyclohexane mixture. M. p. 120 ◦C (Lit. [17]: 120 –
◦
121 C). – 1H NMR (400 MHz, CDCl3): δ = 7.05 (dt, 2H),
7.12 (t, 1H), 7.15 (t, 2H), 7.25 – 7.27 (m, 5H), 7.30 (t, 1H),
7.37 (dt, 2H), 7.42 (t, 1H), 7.58 (d, J = 10.0 Hz, 1H), 7.73
(dd, J = 11.2, J = 4 Hz, 2 H).
7-(4-Chlorobenzyl)-benzo[a]acridiniumperchlorate (15e)
in a yield of 96 %. M. p. 299 – 300 ◦C. – 1H NMR (400 MHz,
CF3COOH): δ = 6.62 (s, 2H, CH2), 7.13 (d, J = 11.2 Hz,
2H), 7.42 (d, J = 11.2 Hz, 2H), 8.01 (t, 1H), 8.11 – 8.22 (m,
4H), 8.36 (m, 2H), 8.67 (t, 2H), 9.09 (d, J = 10.8 Hz, 1H),
10.49 (s, 1H). – MS ((+)ESI): m/z = 354.2, 355.1−, 356.1,
357.1 (calcd. 354.85 for C24H17ClN+, [M–ClO4 ]+). –
C24H17Cl2NO4 (454.30): calcd. C 63.45, H 3.77, Cl 15.61,
N 3.08, O 14.09; found C 63.49, H 3.31, N 3.20.
Preparation of the benz[a]acridinium perchlorates 15
(General procedure)
To a solution of N-phenyl-2-naphthylamine (11, 2.2 g,
10 mmol) in DMF (25 mL) the corresponding alkylating
reagent R-X (1◦5 mmol) was added and the resulting mixture
heated at 120 C for 30 min. After cooling, POCl3 (3.2 g,
20 mmol) was added dropwise to the reaction mixture which
◦
was subsequently heated at 90 C for 2 h and then cooled
7-(1-Naphthylmethyl)-benz[a]acridinium perchlorate
(15f) in a yield of 90 %. M. p. 297 – 300 ◦C. – 1H NMR
(400 MHz, CF3COOH): δ = 7.07 (s, 3H, CH2), 7.79 (t, 1H),
7.90 (t, 1H), 7.97 – 8.20 (M, 7H), 8.29 (d, J = 4.8 Hz, 2H),
8.35 (d, J = 10.8 Hz, 1H), 8.57 (d, J = 12.8 Hz, 1H), 8.73 (d,
J = 11.2 Hz, 1H), 9.15, d, J = 11.6 Hz, 1H), 10.57 (s, 1H). –
MS ((+)ESI): m/z = 370.2 (calcd. 370.47 for C28H20N+, [M–
to r. t. After addition of methanol (50 mL), perchloric acid
(70 %, 2 mL) was added to the resulting mixture under cool-
ing. The precipitate formed after addition of some ethyl ac-
etate was isolated by suction and recrystallised, after drying
at air, from acetic acid. The following benz[a]acridinium per-
chlorates were prepared:
7-Methyl-benzo[a]acridinium perchlorate (15a) in a yield ClO−]+). – C18H14ClNO4 (469.92): calcd. C 71.57, H 4.29,
Cl 74.54, N 2.98, O 13.62; found C 71.30, H 4.37, N 3.00.
of 80 %. M. p. 320 – 324 ◦C. – 1H NMR (400 MHz,
CF3COOH): δ = 5.32 (s, 3H, CH3), 8.35 (t, 1 H), 8.46 (t,
2 H), 8.56 (d, J = 10.0 Hz, 1H), 8.70 – 8.81 (m, 2H), 8.95
(dd, J = 12.8 Hz, J = 4.0 Hz, 2H), 9.08 (d, J = 12.8 Hz, 1H),
9.39 (d, J = 10.8 Hz, 1 H), 10.76 (s, 1H). – MS ((−+)ESI):
m/z = 244.0 (calcd. 244.31 for C18H14N+, [M–ClO4 ]+). –
C18H14ClNO4 (343.76): calcd. C 62.89, H 4.10, Cl 10.31,
N 4.20, O 18.62; found C 62.44, H 4.18, N 4.20.
7-Phenyl-benz[a]acridinium perchlorate (15g) in a yield
◦
1
of 82 %. M. p. 335 C. – H NMR (400 MHz, CF3COOH):
δ = 7.37 (d, J = 12.8 Hz, 1H), 7.49 (d, J = 12.0 Hz, 1H),
7.82 – 7.86 (m, 2H), 8.02 (d, J = 9.6 Hz, 1H), 7.95 – 7.98 (m,
3H), 8.10 – 8.19 (m, 2H), 8.25 – 8.31 (m, 2H), 8.64 (d, J =
12.8 Hz, 1H), 8.80 (dd, J = 10.8 Hz, 1H). – MS ((−+)ESI):
m/z = 306.1 (calcd. 306,38 for C23H16N+, [M–ClO4 ]+). –
7-Ethyl-benzo[a]acridinium perchlorate (15b) in a yield C23H16ClNO4 (405.83): calcd. C 68.07, H 3.97, Cl 8.74,
◦
1
of 86 %. M. p. 293 C. – H NMR (400 MHz, CF3COOH): N 3.45, O 15.77; found C 68.01, H 3.97, N 3.52.
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