New photochromes equipped with positively charged ammonium fragments

Article abstract of DOI:10.1016/j.mencom.2015.09.018

Quaternization of N-heterocycle-fused chromenes with iodomethane and of triethylamine with 3-bromopropyl-substituted spiro- naphthoxazine affords new ammonium-equipped photochromes.

Full text of DOI:10.1016/j.mencom.2015.09.018

Mendeleev
Communications
Mendeleev Commun., 2015, 25, 370–371
New photochromes equipped with positively
charged ammonium fragments
Vladimir Lokshin,a Sergey V. Paramonovb and Olga A. Fedorova*b
a Aix-Marseille Université, CNRS, CINaM UMR 7325, 13288 Marseille, France. Fax: +33 4 9182 9301;
e-mail: lokshin@cinam.univ-mrs.fr
b A. N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, 119991 Moscow,
Russian Federation. Fax: +7 499 135 5085; e-mail: fedorova@ineos.ac.ru
DOI: 10.1016/j.mencom.2015.09.018
Quaternization of N-heterocycle-fused chromenes with iodomethane and of triethylamine with 3-bromopropyl-substituted spiro-
naphthoxazine affords new ammonium-equipped photochromes.
Photochromic benzo- and naphthopyrans are promising for
reversible photocontrol of DNA intercalation. In the initial state,
these compounds are colourless. Nonplanarity of their molecules
is maintained by the presence of two phenyl substituents in the
pyran moiety. One may expect that before irradiation, due to
spatial hindrances, no noticeable interaction with DNA should
occur.1–7 Upon irradiation, the photochrome molecule is trans-
formed into a planar open form which seems capable of inserting
between DNA base pairs. For small aromatic compounds, the
presence of positive charge in a molecule is required to provide
interaction with DNA, which is important for designing new
chemotherapeutic agents and health safe DNA labels.8
A goal of this study was a synthesis of new positively charged
photochromic compounds capable of photocontrolled DNA inter-
calation. We were aiming to obtain quaternary ammonium salts
from N-heterocycle-fused chromenes 1–5 (Scheme 1) and from
3-bromopropyl-containing spironaphthoxazine 8 (Scheme 2).†
Known9–11 heterocyclic chromenes 1–5 were prepared by
titanium tetraethoxide-assisted condensation of the correspond-
ing phenolic derivatives with b,b-diphenylacrolein in fair to
good yields (see Scheme 1). For their N-quarternization, iodo-
methane was used. The reaction was carried out in excess of MeI
in a closed ampoule at ~60°C. In cases of reactants 2, 3 and 5,
the target salts were not obtained. The N-atom in compounds
2–5 possesses lower basicity compared to that of compound 1.
This fact explains the fair yield of product 6 and moderate yield
of product 7. In case of chromenes 2, 3 and 5, one can suppose
that steric hindrance can also hamper the N-methylation. The
structure of chromene 4 was confirmed by X-ray analysis‡
(Figure 1 and Online Supplementary Materials).
Spironaphthoxazine salt 9 was prepared in three steps (see
Scheme 2).† Its key precursor 8 was synthesized from 2,3,3-
trimethylindoline and 1,3-dibromopropane (cf. ref. 1) through
obtaining quaternary indoline salt 10 along with cyclic side
product 11. Heterocyclization of compound 10 with 1-nitroso-
naphthalen-2-ol gave the spiro derivative 8 in only 10% yield.
Final reaction of compound 8 with triethylamine afforded the
target salt 9 in 38% yield.
†
General procedure for the synthesis of 6, 7. In a thick-walled glass tube
equipped with a threaded teflon stopper, 0.158 mmol of 1 or 4 and 2 ml
of iodomethane were mixed. The solution obtained was stirred at 60°C
for 3 h. Then, the solvent was removed; and the residue was treated with
diethyl ether to yield salt 6 or 7 as yellow solids.
9-Methyl-3,3-diphenyl-3H-pyrano[2,3-h]isoquinolinium iodide 6: yield
87%, mp 218–222°C. 1H NMR (CDCl3) d: 4.80 (s, 3H, NMe), 6.56 (d,
1H, H-2, J 10.1 Hz), 7.20–7.48 (m, 10H), 7.71 (d, 1H, J 8.9 Hz), 7.83
(d, 1H, J 8.9 Hz), 7.97–8.17 (m, 3H), 10.97 (s, 1H, H-10). Found (%):
C, 63.52; H, 4.28. Calc. for C25H20INO (%): C, 62.90; H, 4.22.
Ph
Ph
Ph
Ph
O
Ph
I–
O
OH
O
Ph
MeI
Het
Het
Het
Ti(OEt)4,
toluene, 100 °C
Me
1–5
6, 7
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Me
Ph
Ph
O
O
O
O
O
O
O
N
O
N
O
N
N
Me
Me
Me
Het
N
N
1, 45%
2, 54%
3, 27%
Ph
Ph
4, 33%
5, 28%
Ph
Me
Ph
Ph
Ph
I-
O
O
I–
O
Me
O
Me
N
N
Het
I–
Me
Me
7, 36%
6, 87%
Scheme 1
© 2015 Mendeleev Communications. Published by ELSEVIER B.V.
on behalf of the N. D. Zelinsky Institute of Organic Chemistry of the
Russian Academy of Sciences.
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Mendeleev Commun., 2015, 25, 370–371
Me
Me
Me
N
Me
N
Me
Me
Me
C(21)
Br
Br
C(20)
C(22)
C(23)
Me
+
C(12)
C(8)
EtOH
N
Br–
10
Br–
11
C(24)
C(13)
C(19)
C(6)
O(1)
C(5)
C(18)
C(9)
C(10)
O(2)
Br
C(17)
C(16)
i, NaOH, CH2Cl2
NO
C(1)
N(1)
C(7)
C(14)
C(11)
Me
Me
C(4)
OH
C(2)
C(3)
ii,
, MeOH
C(15)
N
N
10
O
Figure 1 Molecular structure of chromene 4.
R
Salts 6, 7 and 9 are well soluble in polar organic solvents
8 R = Br, 10%
9 R = Et3N+Br–, 38%
Et3N,
benzene
and water. Optical investigation showed that compound 6 is
fl
fluorescent (l
395 nm in MeCN, lex 313 nm), and does not
max
exhibit photochromism (see Figure S1 in Online Suplementary
Materials). In contrast, benzoxazole derivative 7 exhibits good
photochromic properties (colorability upon cessation of radia-
tion) in polar acetonitrile and methanol (Figure 2),§ which is
unusual for chromenes.12 The values of the bleaching rate con-
stant k is 1.02×10–3 s–1, the half bleaching time t1/2 is 680 s.
Spironaphthoxazine 9 demonstrates the photochromic properties;
however, the stability of the open form in aqueous solutions at
Scheme 2
3
2
1
0
200
300
400
500
600
700
l/nm
1,2,4-Trimethyl-6,6-diphenyl-6H-chromeno[6,7-d]oxazolium iodide 7:
yield 36%, mp 245–247°C. 1H NMR (CDCl3) d: 2.45 (s, 3H, 4-Me), 3.29
(s, 3H, 2-Me), 4.25 (s, 3H, 1-Me), 6.34 (d, 1H, H-7, J 10.0 Hz), 6.82 (d, 1H,
H-8, J 10.0 Hz), 7.24–7.47 (m, 11H). 13C NMR (63 MHz, CDCl3) d: 8.88,
22.30, 36.46, 82.77, 114.02, 114.27, 122.14, 122.89, 123.41, 126.38, 126.76,
126.81, 127.41, 127.49, 128.16, 145.30, 151.19, 151.76, 173.22, 181.68.
Found (%): C, 60.92; H, 4.53. Calc. for C25H22INO2 (%): C, 60.62; H, 4.48.
{3-[3,3-Dimethylspiro(indoline-2,3'-[3H]naphtho[2,1-b][1,4]oxazin)-
1-yl]propyl}triethylammonium bromide 9. Spironaphthoxazine 8 (0.053 g,
0.122 mmol) [prepared from 1-(3-bromopropyl)-2,3,3-trimethyl-3H-indo-
lium iodide1] and freshly distilled triethylamine (0.123 g, 1.22 mmol) were
dissolved in 5 ml of dry acetonitrile. The solution was stirred at 60°C for
24 h. Then, the solvent was removed under reduced pressure and the
residue was treated with diethyl ether to afford 0.025 g (38%) of salt 9 as
creamy-beige solid, mp 218–220°C. 1H NMR (DMSO-d6) d: 1.08 (t, 9H,
3CH2Me, J 7.1 Hz), 1.26 (s, 3H, Me), 1.30 (s, 3H, Me), 1.75–1.88 (m,
1H, CH2), 1.98–2.11 (m, 1H, CH2), 3.10–3.27 (m, 10H), 6.81 (d, 1H,
J 7.8 Hz), 6.86 (dd, 1H, J 7.4 Hz), 7.10–7.22 (m, 3H), 7.43 (dd, 1H,
J 7.6 Hz), 7.60 (dd, 1H, J 7.6 Hz), 7.82 (d, 1H, J 8.9 Hz), 7.86 (d, 1H,
J 8.2 Hz), 7.97 (s, 1H), 8.49 (d, 1H, J8.4 Hz). 13C NMR (150 MHz, DMSO-d6)
d: 7.02, 20.55, 20.68, 25.12, 40.80, 51.73, 52.11, 53.72, 98.68, 106.90,
106.92, 116.63, 119.63, 120.97, 121.72, 122.00, 124.17, 127.15, 127.78,
127.82, 128.89, 130.12, 130.30, 135.21, 143.17, 146.14, 151.69. Found (%):
C, 67.32; H, 7.20. Calc. for C30H38BrN3O (%): C, 67.16; H, 7.14.
Figure 2 Absorption spectra of compound 7 in methanol (C = 66.5 mmol dm–3
20°C) prior to (solid line) and after 1 min of irradiation by monochromatic
,
light with l = 315 nm (dashed line).
20°Cwaslow.Nevertheless,basedonphotochromiccharacteristics
both 7 and 9 photochromes can be considered as appropriate
candidates for testing as photoswitchable intercalators for DNA.
This study was supported by the Russian Foundation for Basic
Research and French National Centre for Scientific Research
(joint grant no. 13-03-93106).
Online Supplementary Materials
Supplementary data associated with this article can be found
in the online version at doi:10.1016/j.mencom.2015.09.018.
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§
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Received: 20th January 2015; Com. 15/4546
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