Novel Synthesis of a New Class of Strongly Fluorescent Phenanthridine Analogues

Article abstract of DOI:10.1039/a606232f

A novel synthesis of strongly fluorescent phenanthridine and phenanthrene analogues as a possible new class of laser dyes utilizing the reactions of tetralin-1-ylidenecyanothioacetamide or tetralin-1-ylidenemalononitrile with β-(2-furyl)- and β-(2-thienyl)-acrylonitriles is reported.

Full text of DOI:10.1039/a606232f

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112 J. CHEM. RESEARCH (S), 1996
J. Chem. Research (S),
1997, 112–113†
Novel Synthesis of a New Class of Strongly Fluorescent
Phenanthridine Analogues†
Galal E. H. Elgemeie,*a Adel M. E. Attiab and Nahed M. Fathyc
aChemistry Department, Faculty of Science, Helwan University, Helwan, Cairo, Egypt
bChemistry Department, Faculty of Education, Tanta University, Tanta, Egypt
cPhotochemistry Department, National Reseach Centre, Dokki, Cairo, Egypt
A novel synthesis of strongly fluorescent phenanthridine and phenanthrene analogues as a possible new class of laser
dyes utilizing the reactions of tetralin-1-ylidenecyanothioacetamide or tetralin-1-ylidenemalononitrile with b-(2-furyl)- and
b-(2-thienyl)-acrylonitriles is reported.
Continuing our interest in the development of efficient and
simple procedures for the synthesis of antimetabolites,1–3 we
have recently reported successful syntheses of sulfanyl purine
and 3-deazapyrimidine nucleosides and of folic acid ana-
logues.4–6 Here we report novel syntheses of phenanthridine
analogues and their condensed derivatives as a possible new
class of laser dye. It was found that tetralin-1-ylidenecyano-
thioacetamide 1b reacted with b-(2-furyl)- and b-(2-thienyl)-
methylidenemalononitriles 2a,b in refluxing ethanol contain-
ing catalytic amounts of piperidine for 3 h to give the
unexpected phenanthridine analogues 4 (Scheme 1).
The formation of 4 from 1b and 2a,b is assumed to proceed
via addition of the active methylene group of 1b to the double
bond of 2a,b to give Michael intermediates which then cyclize
via malononitrile elimination and oxidation under the reac-
tion conditions to yield 4. The unexpected course of the
reaction between the b-(2-furyl)- and b-(2-thienyl)-methyli-
denemalononitriles 2a,b and 1b prompted us to investigate
the reaction between the tetralin-1-ylidenemalononitrile 1a
and b-(2-furyl)- and b-(2-thienyl)-methylidenecyanothioacet-
amides 2c,d under the same reaction conditions. The
products 4 obtained were shown to be the same as those
obtained from the reaction of 1b with 2a,b by TLC, melting
point and spectral data. The mechanism of the reaction of 1a
and 2c,d is assumed to proceed through the exchange reac-
tion between the cycloalkylidene group of 1a and the arylme-
thylidene group of 2c,d, followed by Michael addition which
leads to the intermediate 3 and hence to the final product 4 as
produced by the reaction of 1b with 2a,b.
NC
Z
For 1b, 2a, b
For 1a, 2c, d
Y
+
(1) Exchange reaction
(2) Michael addition
(1) Michael addition
(2) –CH2(CN)2
(3) –H2
X
CN
2a X = O, Y = CN
X = S, Y = CN
b
1a Z = CN
b Z = C(C S)NH2 c X = O, Y = C(C S)NH2
d X = S, Y = C(C S)NH2
S
S
NC
CN
NC
NC
–CH2(CN)2
–H2
NH
NH2
We studied the reaction of b-(2-furyl)- and b-(2-thienyl)-
1-tetralone 5 with cyanothioacetamide 6. It was found that 5
reacts with 6 in boiling ethanol containing a catalytic amount
of piperidine to give two products (TLC), of which the first
was formulated as the phenanthridine analogues 4 and the
second as the carbocyclic nitriles 9 (Scheme 2).
X
X
3
4
Scheme 1
The products 4 obtained from this reaction were shown to
be the same as those obtained from the reaction of 1 and 2 by
TLC, melting point and spectral data. The mechanism for the
formation of 4 from reaction of 5 and 6 is assumed to proceed
through the formation of the initial adducts 7, which cyclized
and oxidized under the reaction conditions to yield 4. The
mechanism for the formation of 9 from the reaction of 5 and
6 is assumed to proceed via addition of the active methylene
group of 6 to the double bond of 5 to give intermediate 8.
This Michael adduct then cyclizes via water elimination to
form a 1,4-dihydrothiopyran species, which undergoes ring
contraction and elimination of ammonia followed by oxida-
tion to give the phenanthrene analogues 9.
O
S
CH
X
EtOH/piperidine
heat
NH2
+
CN
5a X = O
b X = S
6
•
S
•
S
H2N
O
CN
NC
NH2
CH
+
X
X
Table 1 The absorption and emission maxima together with
the ꢀf values in ethanola
8
7
(1) Cyclization
(2) –H2O
(3) –NH3
(1) Cyclization
(2) –H2
Compound
Absorption
maxima/nm
Emission
maxima/nm
ꢀf
(4) –H2
S
CN
9a
381.5, 275.5, 227.0
374.5, 274.0, 227.0
373.0, 282.0, 241.0
366.0, 280.5, 233.0
370.5, 281.0, 243.0
373.5, 272.0, 228.0
369.5, 263.0, 222.5
369.5, 278.5
425
420
410
410
400
420
410
435
410
460
0.35
0.29
0.04
0.03
0.04
0.11
0.99
0.98
0.99
0.99
4
9b
10a
10b
11a
11b
12a
12b
12c
12d
X
9
Scheme 2
367.0, 271.0, 224.5
373.0, 283.0, 229.0
*To receive any correspondence.
†This is a Short Paper as defined in the Instructions for Authors,
Section 5.0 [see J. Chem. Research (S), 1997, Issue 1]; there is there-
fore no corresponding material in J. Chem. Research (M).
aExcitation wavelengths corresponding to the lowest energy
absorption maxima were used.

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J. CHEM. RESEARCH (S), 1997 113
5,6-Dihydrobenzo[f]isoquinoline-2(3H)-thiones 4.sTo a mixture
of 1b and 2a,b or 1a and 2c,d (0.01 mol) in ethanol (50 ml),
piperidine (0.3 ml) was added. The reaction mixture was heated
under reflux for 3 h and then left to stand overnight. The resultant
precipitate was filtered off and crystallized from dioxane to afford
yellow crystals. 4a: mp 200 °C, yield 24%; vmax/cmꢀ1 (KBr) 3280
(NH), 2216 (CN); dH ([2H6]Me2SO) 2.51 (s, 2 H, CH2), 2.82 (s, 2 H,
CH2), 6.82 (d, 1 H, furan 4-H), 7.34 (m, 4 H, Ar-H), 7.94 (d, 1 H,
furan 3-H), 8.06 (s, 1 H, furan 5-H), 13.92 (brs, 1 H, NH); m/z 304
(Found: C, 71.2; H, 4.1; N, 9.0.C18H12N2OS requires C, 71.1; H, 3.9;
N, 9.2%). 4b: mp 276 °C, yield 20%; vmax/cmꢀ1 (KBr) 3300 (NH),
2215 (CN); m/z 320 (Found: C, 67.2; H, 4.0; N, 9.1. C18N12N2S2
requires C, 67.5; H, 3.8; N, 8.8%).
Compounds 4 bearing latent functional substituents were
found useful for the synthesis of fused pyridines. It was found
that 4 reacted with methyl iodide in sodium ethoxide to
afford the corresponding S-alkyl derivatives 10 (Scheme 3).
When salts of 4 were treated with phenacyl bromide as an
alkylating agent, the S-alkylated derivatives were not iso-
lated, but instead gave the cyclized thieno[3,4-b]isoquinoline
derivative 11. Table 1 summarizes some spectral and ꢀf data
for compounds 9–12. Relatively high values are obtained
only in the case of 9a,b, yet the values are much lower than
the phenyl analogues 12, the latter showing very high fluor-
escence efficiencies (ꢀf values as high as 0.99 were obtained
for X = OMe, Me and Cl). This suggests that these deriva-
tives may be potential candidates for laser dyes, solar harvest-
ing dyes, fluorogenic dyes, etc. For compounds 9–11, the
presence of a heteroatom plays a role in fluorescence
quenching. Molecular flexibility in 11a,b also reduces the
fluorescence efficiency by enhancing internal conversion to
the ground state.
1-Thioxo-1H-cyclopenta[a]naphthalene-2-carbonitriles
9.sA
solution of b-(2-furyl)- and b-(2-thienyl)-methylidene-1-tetralone 5
(0.01 mol) and cyanothioacetamide 6 (0.01 mol) in ethanol (30 ml)
and a few drops of piperidine was refluxed for 3 h, cooled, and the
precipitate was filtered off and crystallized from the appropriate
solvent. The first fraction comprised compounds 4. Water (2 ml)
was then added to the filtrate and the formed solid was filtered off
and recrystallized from aqueous ethanol to yield compounds 9. 9a:
mp 152 °C, yield 18%; vmax/cmꢀ1 (KBr) 2218 (CN); dH
([2H6]Me2SO) 6.76 (d, 1 H, furan 4-H), 6.81 (s, 2 H, C6H2),
6.95–7.40 (m, 4 H, C6H4), 7.97 (d, 1 H, furan 3-H), 8.16 (d, 1 H,
furan 5-H); m/z287 (Found: C, 75.5; H, 3.3; N, 5.1. C18H9NOS
SCH2R
NC
requires C, 75.3; H, 3.1; N, 4.9%). 9b: mp 189 °C, yield 21%; vmax
/
cmꢀ1 (KBr) 2216 (CN); m/z 303 (Found: C, 71.0; H, 3.4; N, 4.5.
C18H9NS2 requires C, 71.3; H, 3.0; N, 4.6%).
N
RCH2X
–HX
4
5,6-Dihydro-2-(methylsulfanyl)benzo[f]isoquinoline 10.s5,6-Di-
hydrobenzo[f]isoquinoline-2(3H)-thione 4 (0.0017 mol) was sus-
pended in a solution of sodium ethoxide (from 0.0051 mol of
sodium) in ethanol (25 ml). An excess of methyl iodide (0.0028
mol) was added dropwise to the resulting mixture. The precipitate
obtained after 2 h stirring at room temperature was filtered off and
recrystallized from ethanol to afford yellow crystals. 10a: mp
153 °C, yield 63%; vmax/cmꢀ1 (KBr) 2215 (CN); lmax/nm 285, 298,
316 and 346; m/z 318 (Found: C, 71.5; H, 4.6; N, 9.0. C19H14N2OS
a R = H
b R = COPh
X
10a X = O, R = H
b X = S, R = H
R
S
S
CN
requires C, 71.7; H, 4.4; N, 8.8%). 10b: mp 171 °C, yield 60%; vmax/
cmꢀ1 (KBr) 2218 (CN); m/z 334 (Found: C, 68.1; H, 4.5; N, 8.3.
C19H14N2S2 requires C, 68.3; H, 4.2; N, 8.4%).
H2N
N
6,7-Dihydrobenzo[f]thieno[3,4-b]isoquinoline 11.sA mixture of
4 (0.01 mol), sodium ethoxide (0.01 mol) and phenacyl bromide
(0.01 mol) in dry ethanol (50 ml) was refluxed for 3 h and then
allowed to cool to room temperature and acidified with cold dilute
hydrochloric acid. The resulting solid product was collected by
filtration and recrystallized from ethanol to afford yellow crystals.
11a: mp 193 °C, yield 57%; vmax/cmꢀ1 (KBr) 3400, 3280 (NH2), 1700
(CO); dH ([2H6]Me2SO) dH 2.76 (s, 2 H, CH2), 2.88 (t, 2 H, CH2),
6.41 (s, 2 H, NH2), 6.88 (m, 1 H, furan 4-H), 7.22–7.94 (m, 9 H,
C6H5 and C6H4), 8.20 (d, 1 H, furan 3-H), 8.28 (d, 1 H, furan 5-H);
m/z 422 (Found: C, 73.6; H, 4.0; N, 6.8. C26H18N2O2S requires C,
73.9; H, 4.3; N, 6.6%). 11b: mp 180 °C, yield 56%; vmax/cmꢀ1 (KBr)
3450, 3285 (NH2), 1690 (CO); dH ([2H6]Me2SO) dH 2.62 (t, 2 H,
CH2), 2.69 (t, 2 H, CH2), 6.83 (s, 2 H, NH2), 7.24 (m, 10 H, C6H5,
C6H4 and furan 4-H), 7.78 (d, 1 H, furan 3-H), 8.17 (d, 1 H, furan
5-H); m/z 438 (Found: C, 71.4; H, 4.3; N, 6.6. C26H18N2OS2 requires
C, 71.2; H, 4.1; N, 6.4%).
X
X
12a X = Cl
b X = Me
c X = OMe
d X = NMe2
11a X = O, R = COPh
b X = S, R = COPh
Scheme 3
Experimental
Melting points are uncorrected. For TLC aluminium sheets
[silica-gel 60 F254 (Merck)] were used. Detection was effected by
viewing under a short-wavelength UV lamp. IR spectra were
1
obtained (KBr discs) on a Pye Unicam Spectra-1000. H NMR
were measured on a Wilmad 270 MHz or on a Varian 400 MHz
spectrometer for solutions in (CD3)2SO using SiMe4 as internal
standard. Mass spectra were recorded on a Varian MAT 112 spec-
trometer. Analytical data were obtained from the Microanalytical
Data Center at Cairo University. Emission and excitation spectra,
together with fluorescence quantum yields (ꢀf) were measured
using a Shimadzu RF 510 spectrofluorophotometer connected to
Received, 10th September 1996; Accepted, 22nd October 1996
Paper E/6/06232F
References
an ultrathermostat (Julabo
F 10) of temperature precision
<0.1 °C. ꢀf was measured relative to 9,10-diphenylanthracene as a
reference standard7 applying low concentrations to avoid reabsorp-
tion. The following relation was applied to calculate the fluor-
escence quantum yields ꢀf(s) relative to the fluorescence quantum
yield of 9,10-diphenylanthracene, ꢀf(r):
1 G. E. H. Elgemeie, A. M. E. Attia, D. S. Farag and S. M. Sherif,
J. Chem. Soc., Perkin Trans. 1, 1994, 1285.
2 G. E. H. Elgemeie and B. A. Hussain, Tetrahedron, 1994, 50,
199.
3 G. E. H. Elgemeie, S. E. Elezbawy, H. A. Ali and A. K. Mansour,
Bull. Chem. Soc. Jpn., 1994, 67, 738.
ZIs(u)du Ar ns2
ꢀf(s):ꢀf(r)
4 G. E. H. Elgemeie, A. M. E. Attia, A. M. Elzanate and A. K.
Mansour, Bull. Chem. Soc. Jpn., 1994, 67, 1627.
5 G. E. H. Elgemeie, N. M. Fathy, L. M. Faddah, M. K. Elsaid and
M. Y. Ebeid, Arch. Pharm., (Weinheim, Ger.), 1991, 324, 149.
6 G. E. H. Elgemeie, A. M. E. Attia and N. M. Fathy, Liebigs Ann.
Chem., 1994, 955.
s nr2
ZIr(u)du A
where the integrals represent the corrected fluorescence peak
areas. A and n are the absorbance at the excitation wavelengths and
the refractive index of the applied solvents respectively. UV–VIS
absorption spectra were measured using a Shimadzu UV-160 A
spectrophotometer. We have previously described compounds
12.8
7 J. V. Morris, M. A. Mahancy and J. R. Huber, J. Phy. Chem., 1976,
80, 969.
8 G. E. H. Elgemeie and N. M. Fathy, Tetrahedron, 1995, 51, 3345.