9-Isothiocyanatoanthracene as a versatile starting compound in the chemistry of anthracen-9-yl derivatives

Article abstract of DOI:10.1135/cccc20020665

The synthesis, structure and reactivity of 9-isothiocyanatoanthracene (5) likewise the conformation of the corresponding thioureas (6a-6i) have been studied. The ¹³C NMR substituent chemical shift values of the NCS group and correlations betwee

Full text of DOI:10.1135/cccc20020665

9-Isothiocyanatoanthracene
665
9-ISOTHIOCYANATOANTHRACENE AS A VERSATILE STARTING
COMPOUND IN THE CHEMISTRY OF ANTHRACEN-9-YL DERIVATIVES
Ladislav JANOVECa1, Gejza SUCHÁRa2, Ján IMRICHa3, Pavol KRISTIANa4,*,
b2
c
Vlasta SASINKOVÁb1, Juraj ALFÖLDI and Erik SEDLÁK
a
Department of Organic Chemistry, Faculty of Science, P. J. Šafárik University,
SK-04167 Košice, Slovak Republic; e-mail: janovec@kosice.upjs.sk, sucharg@kosice.upjs.sk,
jimrich@kosice.upjs.sk, kristian@kosice.upjs.sk
Chemical Institute, Slovak Academy of Sciences, SK-84238 Bratislava, Slovak Republic;
e-mail: chemsasi@savba.sk, chemalf@savba.sk
1
2
3
4
b
c
1
2
Department of Biochemistry, Faculty of Science, P. J. Šafárik University, SK-04167 Košice,
Slovak Republic; e-mail: sedlak_er@saske.sk
Received October 29, 2001
Accepted April 8, 2002
Th e syn th esis, structure an d reactivity of 9-isoth iocyan atoan th racen e (5) likewise th e con for-
m ation of th e correspon din g th ioureas (6a–6i) h ave been studied. Th e 13C NMR substituen t
ch em ical sh ift values of th e NCS group an d correlation s between spectral param eters (IR,
NMR) an d rate con stan s of reaction s of 5, acridin -9-yl (14), ph en yl (15) an d ben zoyl
isoth iocyan ate (16) with butylam in e were foun d. Sign ifican t in crease of th e fluorescen ce of
th e syn th esized an th racen ylth ioureas with am in o acid rests refers to th e possibility to use 5
as poten tial biom arker.
Keyw ord s: Isoth iocyan ates; Th ioureas; 9-Isoth iocyan atoan th racen e; An th racen ylth ioureas;
Kin etics; IR spectroscopy; 13C NMR spectroscopy; Fluorescen ce.
Th e h igh ch em ical reactivity of th e NCS group1 in addition an d cyclization
reaction s m ade ch em ists look for various types of isoth iocyan ates as suit-
able startin g com poun ds in th e syn th esis of organ ic derivatives possessin g
ch aracteristic biological an d ph ysicoch em ical properties. In terestin g results
obtain ed in our previous studies regardin g th e syn th esis an d reactivity of
acridin -9-yl derivatives2 prom pted us to prepare an alogous an th racen e
com poun ds. In recen t years a variety of an th racen e derivatives h as received
atten tion as poten tial an titum or drugs3, e.g. bisan tren (9,10-bis substituted
an th racen e) (1). Th ese com poun ds are typical DNA-in tercalatin g agen ts
wh ere th e in h ibition of DNA syn th esis4 is based on th e ability of th e plan ar
an th racen e skeleton to in corporate in to th e stacked base-pairs of DNA dou-
ble h elix. Even som e m on osubstituted an th racen es as am ide derivatives 2
are active again st tum or cells5. An th racen on es such as an th ralin (3) are
Collect. Czech. Chem. Commun. (Vol. 67) (2002)
doi:10.1135/cccc20020665

666
Janovec et al.:
am on g th e m ajor topical rem edies for th e treatm en t of psoriasis6. An oth er
an th racen e derivatives 4 are well-kn own as suitable fluorescen t reagen ts
for labelin g of biom olecules7. In order to obtain n ew fluorogen s an d biolog-
ically in terestin g com poun ds, we looked for a con ven ien t startin g com -
poun d to syn th esize a great variety of an th racen e derivatives. Th e lon g-
tim e experien ce in th e ch em istry of isoth iocyan ates1 in spired us to ch oose
9-isoth iocyan atoan th racen e (5) for th is purpose.
CONH(CH2)2N(CH3)2
H
N
N
N
NH
NH
OMe
N
2
N
OH
O
OH
4
N
H
COOH
H
1
NH2
3
Despite th e fact th at com poun d 5 was syn th esized already in 1966 (ref.8),
n o data are kn own regardin g its use in organ ic syn th esis in th e literature up
to n ow. Th e aim of th is work was to im prove th e syn th esis of 5 an d obtain
n ew in form ation on its ph ysicoch em ical properties, as well as, to study th e
fluorescen ce an d con figuration of syn th esized th iourea derivatives as m odel
fluorescen t com poun ds an d precursors of n ew polycyclic system s.
In th e m ean tim e, we h ave foun d an un expected regioselectivity in th e
reaction of 1-(an tracen -9-yl)-3-alkylth ioureas 6 with brom oacetic acid de-
rivatives to give 2-(an th racen -9-ylim in o)-3-alkyl-1,3-th iazolidin -4-on es 7
an d 3-(an th racen -9-yl)-2-alkylim in o-1,3-th iazolidin -4-on es 8 (refs9,10).
S
S
S
O
R
R
O
N
N
NCS
HN
N
N
N
H
R
5
6
7
8
RESULTS AND DISCUSSION
Th e previously described syn th esis of 9-isoth iocyan atoan th racen e (5) was
carried out by 1,3-dipolar cycloaddition of an th racen e-9-carbon itrile N-ox-
ide (9), prepared from an th racen e-9-carbaldeh yde oxim e (10) an d carbon
Collect. Czech. Chem. Commun. (Vol. 67) (2002)

9-Isothiocyanatoanthracene
667
disulfide in a pressure vessel at 90 °C (ref.8). In order to sim plify it, we h ave
th orough ly tested oth er m eth ods, based on 9-am in oan th racen e (11) an d
9-brom oan th racen e (12), wh ich are usually used for th e syn th esis of aro-
m atic isoth iocyan ates1 (Sch em e 1).
Br
SCN
NCS
(ii)
(i)
13
+
12
13
5
NH2
(iii)
(iv)
5
11
C
N O
HC N OH
(v)
5
9
10
(i) AgSCN, I2, heptane; (ii) KSCN, I2, heptane; (iii) CSCl2, CH2Cl2–H2O, NaHCO3;
(iv) NaOH, NaBrO, H2O–CH3CN; (v) KSCN, CH3OH, CHCl3
SCHEME 1
We foun d out th at 9-brom oan th racen e (12) reacted n eith er with silver
th iocyan ate in toluen e at reflux n or with potassium th iocyan ate in a m ix-
ture dich lorom eth an e–water. Th e reaction of 9-brom oan th racen e (12) with
silver th iocyan ate in h eptan e in th e presen ce of iodin e (i) afforded on ly
15% of 9-isoth iocyan atoan tracen e (5) togeth er with th e m ajor product,
9-th iocyan atoan th racen e (13). Th e reaction with potassium th iocyan ate
un der th e sam e con dition s (ii) yielded on ly th iocyan ate 13, wh ereas
9-am in oan th racen e (11) an d th ioph osgen e yielded (iii) m erely 7% of
isoth iocyan ate 5. However, we succeeded in m odifyin g th e an th racen e-
9-carbon itrile N-oxide m eth od11 by usin g potassium th iocyan ate ((iv), (v))
in stead of carbon disulfide, wh ich obviated th e n eed to use pressure an d
im proved th e yield of 5 (90%).
To disclose th e structure an d polarity of th e NCS group in 5, we studied
its IR an d 13C NMR spectra an d kin etics in relation to 9-isoth iocyan ato-
acridin e (14), ph en yl isoth iocyan ate (15) an d ben zoyl isoth iocyan ate (16)
Collect. Czech. Chem. Commun. (Vol. 67) (2002)

668
Janovec et al.:
(Table I). Th e results of kin etic m easurem en ts of AdN reaction s of isoth io-
cyan ates 5, 14, 15 an d 16 with butylam in e (log k) allowed to estim ate th e
ran ge of reactivity of th e NCS group, wh ich decreased in th e order ben zoyl >
acridin -9-yl > an th racen -9-yl > ph en yl (Table I).
We were also in terested in th e relation between th e reactivity an d spec-
tral ch aracteristics. From com parison of 13C ch em ical sh ifts of th e NCS
group (Table I) follows th at th e NCS carbon in 14 is stron gly desh ielded
(140.8 ppm ) due to th e electron -acceptor effect of th e h eterocyclic n itro-
gen , th ough n ot so m uch as un der th e in fluen ce of th e carbon yl group
in 16 (147.6 ppm ). In con trast, ch em ical sh ifts of th e NCS carbon in 5
(137.5 ppm ) an d 15 (135.2 ppm ) reflect a weaker desh ieldin g by th e
an th racen e or ben zen e rin g. Lin ear relation sh ips between spectral ch arac-
teristics of th e electroph ilic NCS carbon an d th e reactivity of th e NCS group
derived from Table I (log k – νas(NCS), correlation coefficien t r = 0.995;
log k – δ13C(NCS), r = 0.989; log k – δ13C(C-NCS), r = 0.921) con firm ed th e
dom in an ce of polar effects in th e studied com poun ds.
As it is kn own , th e NCS group in teracts with th e ben zen e rin g by th e
+M an d –I effect1. Th e substituen t-in duced ch em ical sh ifts (SCS) of th e
NCS group in 5, 14 an d 15 are sh own an d com pared on e with an oth er in
Table II.
Th e NCS group boun d to th e an th racen -9-yl or acridin -9-yl group, in ac-
cord with its pseudoh alogen ch aracter, sh ields th e ipso carbon an d carbon s
C-8a,9a, resem blin g brom o an d n ot am in o substituen t. Marked sh ieldin g of
TABLE I
Spectral ch aracteristics of isoth iocyan ates 5, 14, 15, 16 an d th e rate con stan ts of th eir reac-
tion with butylam in e in aceton itrile at 25 °C
13C NMR(NCS) 13C NMR(C–NCS)
log k
ν
as(NCS), cm –1
Com poun d
ppm
ppm
k, l m ol–1 s–1
5
14
15
16
2 095
2 060a
2 110
1 896d
137.46
140.80a
135.24c
147.60c
131.40
132.50a
130.94c
161.60c
–0.374
0.423
1.230
16.97b
–0.512
0.304
3.461
2 893f
a
b
c
d
e
f
Ref.12
;
ref.13
;
ref.14
;
ref.15
;
ref.16
;
ref.17
Collect. Czech. Chem. Commun. (Vol. 67) (2002)

9-Isothiocyanatoanthracene
669
carbon s C-1,8 is also observed, wh ereas carbon s C-3 to C-6, C-4a,10a an d
C-10 are practically in sen sitive to th e substituen t effect.
Startin g from com poun d 5, 1-(an th racen -9-yl)-3-substituted th ioureas
6a–6l, as fluorescen t m odel com poun ds an d in term ediates for h etero-
cycles9, h ave been prepared by addition of prim ary an d secon dary am in es
an d L-am in o acids to 5 in dich lorom eth an e (Sch em e 2).
R
R
R
N
8
5
1
4
9a
4a
8a
7
6
2
3
9
10a
10
TABLE II
Th e 13C NMR substituen t ch em ical sh ift values of com poun d 5, 14, 15 an d related deriva-
tives
SCSa
Com poun d
Ph en yl
R
Ref.
C-9
ipso
C-8a,9a C-4a,10a C-10
C-1,8 C-2,7 C-3,6 C-4,5
ortho
meta
para
NCS
NH2
Cl
2.8
19.2
6.4
–2.8
–12.4
0.2
1.0
1.3
–1.2
–9.5
–2.0
–1.0
0.3
18b
19b
19b
19b
1.0
Br
–5.4
–4.0
11.7
1.9
3.3
2.2
9-An th ryl
NCS
NH2
Cl
–5.1
–7.1
–3.4
–0.5
–7.8
–6.8
–6.0
–0.5
2.0
–1.6
1.4
0.8
–0.2
0.3
0.7
0.8
0.3
0.4
0.1
–0.2
0.1
0.7
–4.0
–13.4
–2.8
–1.1
–5.0
–12.9
–2.5
–0.7
–0.4
0.5
–9.9
–0.2
0.9
20b
20b
20b
21b
22c
21b
22c
0.2
Br
1.8
0.3
–3.9
–3.7
14.4
4.8
0.5
Acridin -9-yl NCS
1.1
2.0
–0.4
0.5
NH2
Cl
–2.3
1.0
–0.4
1.8
–0.4
–0.2
Br
1.1
0.4
–5.2
a
SCS (in ppm ) = 13C ch em ical sh ifts of respective carbon s of R-substituted com poun ds
m in us 13C ch em ical sh ifts of th e com poun d with R = H.
Solven t CDCl3.
Solven t
b
c
DMSO-d6.
Collect. Czech. Chem. Commun. (Vol. 67) (2002)

670
Janovec et al.:
S
H
R2
R1
NCS
N
N
R2
R1
+
H
N
5
6a-6l
a
b
c
d
e
f
g
h
i
6
R1
R2
H
H
H
H
H
H
methyl
ethyl propyl
ethyl propyl butyl tert-butyl sec-butyl furfuryl cyclohexyl ethyl propyl
j
l
k
HNR1R2
Gly
Phe
Ala
SCHEME 2
Th e reaction of 5 with an ilin e in dich lorom eth an e did n ot provide th e
expected th iourea. Th e sam e reaction un der reflux in aceton itrile, wh ich
en h an ced an an alogous reaction of ph en yl isoth iocyan ate with an ilin e ap-
proxim ately six tim es com pared with dich lorom eth an e23, afforded on ly a
low yield of th e correspon din g th iourea.
It is kn own th at 1-arylth ioureas 17a an d 1-aryl-3-alkylth ioureas 17b
adopt E con form ation on th e (aryl–)N–C(=S) bon d24,25. Th e reason is th e
stabilization of th e E isom er on ly by in tram olecular in teraction of th e N′H
proton with a π-orbital of th e arom atic rin g (Fig. 1).
We h ave studied th e con form ation of 1-(an th racen -9-yl)-3-alkyl-
substituted th ioureas 6a–6f by IR spectroscopy in tetrach lorom eth an e
usin g a Magn a System 750 spectroph otom eter an d con firm ed th e sam e E
S
S
H
R
H
H
'
N
'
N
N
N
H
H
E
E
17b
17a
IR (CCl4): ν(NH) = 3 420, νas(N′H2) = 3 521, νs(N′H2) = 3 398
R = sec-butyl: ν(NH) = 3 419, ν(N′H) = 3 389
R = tert-butyl: ν(NH) = 3 415, ν(N′H) = 3 388
FIG. 1
Stabilization of E con form ation in com poun ds 17a, 17b an d its in fluen ce on IR spectra
Collect. Czech. Chem. Commun. (Vol. 67) (2002)

9-Isothiocyanatoanthracene
671
con form ation . Sim ilarly to 1-ph en yl-3-alkylth ioureas25, th e ν(NH) ban d at a
h igh er wavelen gth (3 402–3 404 cm –1), wh ose position is in sen sitive to th e
ch an ge of th e 3-substituen t, can be attributed to th e an th racen e N–H bon d
wh ereas th e absorption ban d at 3 373–3 394 cm –1 to th e alkyl N′–H bon d.
In th ree substituted th ioureas 6g–6i, stabilization by th e h ydrogen bon d
can n ot occur. Th erefore, two absorption ban ds observed for th ese com -
poun ds, on e above 3 400 cm –1 assign ed in accord with ref.25 to th e E isom er
an d th e oth er below 3 400 cm –1 assign ed to th e Z isom er, eviden ce th at
both possible isom ers are presen t. An approxim ate ratio of isom ers can be
assessed from th e in ten sity of respective ban ds: in 6i, th e in ten sity of both
ban ds is equal, 6g sh ows th e m ore in ten sive absorption ban d of th e Z iso-
m er at 3 373 cm –1 an d 6h of th e E isom er at 3 417 cm –1 (Fig. 2).
R1
N
R2
S
S
N
H
R
H
R2
N
N
H
N
N
R1
H
S
E
E
Z
6a-6f
6g-6i
FIG. 2
Con form ation s of th ioureas 6a–6i
20
15
10
5
0
300
350
400
450
500
Wavelength, nm
FIG. 3
UV-VIS spectra of an th racen e, 9-isoth iocyan atoan th racen e (5) an d 1-alkyl-(3-an th racen e-9-yl)-
th ioureas 6a–6h
Collect. Czech. Chem. Commun. (Vol. 67) (2002)

672
Janovec et al.:
Four typical in ten sive UV ban ds of 6a–6i sh ow a h ypsoch rom ic sh ift of
λm ax in com parison with 5 (Fig. 3, Table III). Figure 4 depicts fluorescen ce
spectra of com poun ds 5, 6a–6h an d an th racen e.
Each of th e syn th esized com poun ds 6a–6l except of th e th ioureas with
sec-am in orests 6g–6i are ch aracterized by en h an ced in ten sity of fluores-
cen ce accordin g to th e stan dard 5. Th e h igh est fluorescen ce h as been ob-
served in th e case of th e am in oacid derivatives 6j–6l (F/F0 = 35.29–57.11;
TABLE III
UV-VIS an d fluorescen ce properties of an th racen e an d its derivatives 5, 6a–6h , 6j–6l
Absorban ce
Fluorescen ce
λm ax, n m
F, a.u. (F/F0)
Sen sitivity
Fm ax ε385
Efficien cy
ε385
n m
Com p.
λm ax, n m
ε, m l m ol–1 cm –1
×
Fm ax/ ε385
n m
n m
ε, m l m m ol–1cm –1
6a
366.0
9.93
9.02
8.03
8.49
7.70
7.87
8.88
7.29
6.48
7.94
6.83
8.93
16.25
6.69a
435.6
12.7 (7.3)
114.55
83.51
84.90
56.51
24.48
87.11
–
1.40
1.29
1.17
0.95
0.39
1.10
–
365.8
8.84
434.4
10.4 (6.0)
6b
6c
6d
6e
6f
366.0
9.34
436.0
10.0 (5.7)
366.0
8.49
434.8
7.34 (4.2)
367.4
8.73
439.4
3.11 (1.8)
366.0
9.89
433.6
9.81 (5.6)
367.9
8.13
No fluorescen ce
6g
6h
6j
367.8
7.26
No fluorescen ce
–
–
365.2
9.08
428.0
64.0 (37.64)
508.16
409.80
776.91
27.63
2 944.9b
8.06
8.78
9.74
0.105
65.80c
365.2
7.73
432.0
60.0 (35.29)
6k
6l
365.4
10.29
428.0
87.0 (51.17)
410.2
18.89
443.0
1.7 (1.0)
5
An th racen e
355.4
7.27
426.0
440.2 (253.0)
a
b
c
ε374 n m
;
Fm ax × ε374 n m
;
Fm ax/ε374 n m .
Collect. Czech. Chem. Commun. (Vol. 67) (2002)

9-Isothiocyanatoanthracene
673
Table III). No gen eral con clusion s on th e relation between th e structure an d
fluorescen ce of th e prepared com poun ds could be m ade.
Prelim in ary fluorescen ce studies with am in o acid derivatives 6j–6l sh ow
poten tial use of 9-isoth iocyan atoan th racen e (5) as fluorescen ce m arker for
peptides an d protein s. Furth er studies in th is direction s are un der way.
EXPERIMENTAL
Meltin g poin ts were determ in ed on a Koffler h ot-stage apparatus an d are un corrected. Ele-
m en tal an alysis was don e on a Perkin –Elm er an alyzer CHN 2400. Th e reaction course an d
purity of products were followed by th in -layer ch rom atograph y on Silufol plates (Kavalier).
Spots were detected by UV ligh t at λ = 254 n m . Preparative colum n ch rom atograph y was
don e on a Kieselgel Merck 60, type 9385 or 100, th e grain size 250 µm . IR spectra (cm –1
)
were recorded on a Specord 75 IR spectroph otom eter (Zeiss) in ch loroform an d on a Magn a
System 750 spectroph otom eter in tetrach lorom eth an e or in KBr tablets. UV spectra (λ, n m ;
ε, m l m m ol–1 cm –1
) were obtain ed usin g a Specord M42 spectroph otom eter (Zeiss;
con cen tration 5 · 10–5 m ol l–1) an d a Sh im adzu UV spectroph otom eter (1 · 10–6 m ol l–1 in
aceton itrile). Fluorescen ce m easurem en ts (n m ) were perform ed on a Sh im adzu RF-5000
spectroph otom eter in aceton itrile (1 · 10–6 m ol l–1). Em ission spectra were recorded in th e
420–550 n m region at th e excitation wavelen gth 385 n m . Fluorescen ce param eters are th e
averages of 3–6 subsequen t scan s at th e sam e excitation wavelen gth . Fluorescen ce in ten sities
m easured at room tem perature are expressed in arbitrary un its (a.u.). 1H NMR spectra were
m easured on a Tesla BS 587A spectrom eter (80 MHz) an d 13C NMR spectra on a Varian
Gem in i 2000 NMR spectrom eter (75 MHz) at room tem perature. Ch em ical sh ifts are given in
400
6a
12
300
6b
200
6c
10
8
anthracene
100
0
6f
400
450
500
6e
Wavelength, nm
6
4
2
0
6d
5
6g, 6h
400
450
500
550
Wavelength, nm
FIG. 4
Fluorescen ce of an th racen e, 9-isoth iocyan atoan th racen e (5) an d 1-alkyl-(3-an th racen e-9-yl)-
th ioureas 6a–6h
Collect. Czech. Chem. Commun. (Vol. 67) (2002)

674
Janovec et al.:
ppm (δ-scale), couplin g con stan ts (J) in Hz. Sam ples 6j–6l were dissolved in deuterioaceton e
an d 5, 6a–6i in deuterioch loroform with TMS added as an in tern al stan dard.
Kin etic Measurem en ts
Kin etics of reaction s of 9-isoth iocyan atoan th racen e an d ph en yl isoth iocyan ate with
butylam in e was followed by UV spectroscopy on a Specord M42 spectroph otom eter at 25 °C
in aceton itrile. Con cen tration of isoth iocyan ates (5 · 10–5 m ol l–1) an d th at of am in e
(5 · 10–3 m ol l–1) en sured th e pseudo first-order reaction . Th e apparen t rate con stan ts k′ (s–1
)
were determ in ed from th e slope of th e lin ear relation sh ip log [log (A∞/At)] vs tim e t. Th e
values of rate con stan t k (l m ol–1 s–1) were obtain ed by dividin g th e k′ values by con cen tra-
tion of am in e.
Ch em icals
An th racen e-9-carbaldeh yde, 9-brom oan th racen e, 9-n itroan th racen e, am in es an d h ydroxyl-
am in e h ydroch loride were com m ercial products (Aldrich ), purified by crystallization .
Aceton itrile (Avocado) was dried over ph osph orus pen toxide an d distilled. All th e L-am in o
acids used were com m ercial products (Sigm a).
(Z)-An th racen e-9-carbaldeh yde Oxim e (10)
Th e procedure described in refs26,27 was m odified as follows: To a solution of th e aldeh yde
(300 m g, 1.45 m m ol) in eth an ol (7 m l), a solution of h ydroxylam in e h ydroch loride
(101 m g, 1.45 m m ol) in a sm all volum e of water n eutralized with sodium carbon ate (80 m g,
0.75 m m ol) was added. Th e m ixture was refluxed for 15 m in , filtered with ch arcoal, th e
oxim e deposited on stan din g was filtered off an d dried. Yield 95%, m .p. 165–166 °C.
An th racen e-9-carbon itrile N-Oxide (9)
Th e procedure described in ref.11 was m odified as follows: To a solution of sodium h ydrox-
ide (0.56 g, 14 m m ol) in water (15 m l) (Z)-an th racen e-9-carbaldeh yde oxim e (10) (1 g,
4.52 m m ol) in aceton itrile (15 m l) was added. Th is solution was added dropwise at 0 °C to a
water solution (25 m l) of sodium h ypobrom ite prepared from sodium h ydroxide (0.39 g,
9.75 m m ol) an d brom in e (0.115 g, 0.725 m m ol). Th e m ixture was stirred for 15 m in , th e
precipitate of 9 was filtered off an d dried. Yield 90%, m .p. 128–129 °C.
9-Isoth iocyan atoan th racen e (5)
Th e procedure used for preparation of 2,4,6-trim eth ylph en yl isoth iocyan ate28 was m odified
as follows: To a solution of 9 (1 g, 4.5 m m ol) in ch loroform (10 m l), a solution of potassium
th iocyan ate (0.43 g, 4.5 m m ol) in m eth an ol (20 m l) was added an d th e product 5 deposited.
Solven ts were evaporated un der dim in ish ed pressure an d th e product was purified by col-
um n ch rom atograph y on silicagel (cycloh exan e as a m obile ph ase). Yield 80%, m .p. 138–
139 °C. For C15H9NS (235.3) calculated: 76.56% C, 3.58% H, 5.95% N; foun d: 76.40% C,
3.92% H, 5.94% N. IR: 3 094, 3 064, 3 015 (C-H); 2095 (NCS); 1 618, 1 580 (C=C). 1H NMR:
8.35 s, 1 H (H-10); 7.38–8.32 m , 8 H (an th racen e). 13C NMR: 137.46 (NCS), 123.01 (C-1,
C-8), 127.32 (C-2, C-7), 126.12 (C-3, C-6), 128.75 (C-4, C-5), 131.40 (C-4a, C-10a), 127.82
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(C-8a, C-9a), 122.16 (C-9), 126.45 (C-10). UV (aceton itrile): 368.8 (3.21), 388.8 (3.41), 410.2
(3.40).
9-Am in oan th racen e (11) was prepared by reduction of 9-n itroan th racen e with tin
dich loride in acetic acid an d h ydroch loric acid accordin g to ref.29. 1-Butyl-3-ph en ylth iourea
was prepared from ph en yl isoth iocyan ate an d butylam in e in eth an ol30 an d a stan dard sam -
ple of 9-th iocyan atoan th racen e (13) accordin g to ref.31
.
Preparation of 1-Alkyl-3-(an th racen -9-yl)th ioureas 6a–6i.
Gen eral Meth od
To a solution of 5 (100 m g, 0.425 m m ol) in dich lorom eth an e (5 m l), an equim olar am oun t
of correspon din g am in e was added. After th e en d of reaction (TLC), dich lorom eth an e was
distilled off at reduced pressure an d th iourea was crystallized from dich lorom eth an e–
h eptan e.
1-(Anthracen-9-yl)-3-ethylthiourea (6a): Yield 86%, m .p. 195–196 °C. For C17H16N2S (280.4)
calculated: 72.82% C, 5.75% H, 9.99% N; foun d: 72.54% C, 5.63% H, 9.62% N. IR (CHCl3):
3 395 (NH); 1 606 (C=C); 1 525, 1 477, 1 100 (NHCS). IR (CCl4): 3 404 ν(E)(NH), 3 390
ν
(Z)(NH). 1H NMR: 8.50 s, 1 H (H-10); 7.38–8.31 m , 8 H (an th racen yl); 5.33 bs, 1 H (NH);
3.50 q, 2 H, J = 6.1 (CH2); 0.93 t, 3 H, J = 6.1 (CH3). 13C NMR: 181.80 (C=S); 128.82, 127.70,
126.13, 122.91 (C-1 to C-8); 131.87 (C-4a, 10a); 129.17 (C-8a, 9a); 127.10 (C-9); 128.59
(C-10); 40.39 (CH2); 14.37 (CH3).
1-(Anthracen-9-yl)-3-propylthiourea (6b ): Yield 84%, m .p. 185–187 °C. For C18H18N2S
(294.4) calculated: 73.44% C, 6.16% H, 9.51% N; foun d: 73.17% C, 6.26% H, 9.72% N. IR
(CHCl3): 3 395 (NH); 1 622, 1602 (C=C); 1 520, 1 345, 1 100 (NHCS). IR (CCl4): 3 404
ν
(E)(NH), 3 394 ν(Z)(NH). 1H NMR: 8.54 s, 1 H (H-10); 7.38–8.34 m , 8 H (an th racen yl);
5.38 bs, 1 H (NH); 3.25–3.75 m , 2 H (N-CH2); 1.38 m , 2 H (CH2); 0.93 t, 3 H, J = 7.4 (CH3).
1-(Anthracen-9-yl)-3-butylthiourea (6c): Yield 68%, m .p. 181–183 °C. For C19H20N2S (308.5)
calculated: 73.99% C, 6.54% H, 9.08% N; foun d: 74.01% C, 6.61% H, 9.23% N. IR (CHCl3):
3 405 (NH); 1 622, 1 588 (C=C); 1 522, 1 347, 1 100 (NHCS). IR (CCl4): 3 404 ν(E)(NH), 3 392
ν
(Z)(NH). 1H NMR: 8.47 s, 1 H (H-10); 7.25–8.33 m , 8 H (an th racen yl); 5.33 bs, 1 H (NH);
3.25–3.68 m , 2 H (N-CH2); 0.50–1.50 m , 7 H (CH3CH2CH2). MS (m/z, % rel. in t.): 308 (24)
[M• +], 251 (23) [M• + – C4H9], 235 (47) [M• + – C4H9NH2], 210 (35), 192 (100) [C14H10N], 165
(45).
1-(Anthracen-9-yl)-3-tert-butylthiourea (6d ): Yield 67%, m .p. 195–197 °C. For C19H20N2S
(308.5) calculated: 73.99% C, 6.54% H, 9.08% N; foun d: 74.22% C, 6.31% H, 9.35% N. IR
(CHCl3): 3 370 (NH); 1 630 (C=C); 1 535, 1 510, 1 132 (NHCS). IR (CCl4): 3 404 ν(E)(NH),
3 375 ν(Z)(NH). 1H NMR: 8.51 s, 1 H (H-10); 7.38–8.17 m , 8 H (an th racen yl); 5.33 bs, 1 H
(NH); 1.30 s, 9 H (3 × CH3).
1-(Anthracen-9-yl)-3-sec-butylthiourea (6e): Yield 62%, m .p. 186–187 °C. For C19H20N2S
(308.5) calculated: 73.99% C, 6.54% H, 9.08% N; foun d: 73.70% C, 6.31% H, 9.30% N. IR
(CHCl3): 3 405, 3 375 (NH); 1 625, 1 602 (C=C); 1 510, 1 475, 1 155 (NHCS). IR (CCl4): 3 402
ν
(E)(NH), 3 373 ν(Z)(NH). 1H NMR: 8.51 s, 1 H (H-10); 7.32–8.35 m , 8 H (an th racen yl); 5.00 bs,
1 H (NH); 4.12–4.62 m , 1 H (CH); 1.00–1.47 m , 2 H (CH2); 0.96 d, 3 H, J = 6.8 (CH3); 0.70 t,
J = 7.3 (CH3).
1-(Anthracen-9-yl)-3-furfurythiourea (6f): Yield 71%, m .p. 183–185 °C. For C20H16N2OS
(332.4) calculated: 72.26% C, 4.85% H, 8.43% N; foun d: 72.01% C, 4.93% H, 8.52% N. IR
(CHCl3): 3 392 (NH); 1 605 (C=C); 1 530, 1 475, 1 110 (NHCS). IR (CCl4): 3 402 ν(E)(NH),
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Janovec et al.:
3 392 ν(Z)(NH). 1H NMR: 8.54 s, 1 H (H-10); 7.35–8.30 m , 8 H (an th racen yl); 7.13 bs, 1 H
(H-5-furfuryl); 5.97–6.30 m , 2 H (H-3-furfuryl, H-4-furfuryl); 5.62 bs, 1 H (NH); 4.76 d, 2 H,
J = 5.0 (CH2).
3-(Anthracen-9-yl)-1-cyclohexyl-1-methylthiourea (6g): Yield 88%, m .p. 173–175 °C. For
C
22H24N2S (348.5) calculated: 75.82% C, 6.94% H, 8.04% N; foun d: 76.00% C, 7.10% H,
8.21% N. IR (CHCl3): 3 420, 3 380 (NH); 1 625, 1 600 (C=C), 1 490, 1 445, 1 110 (NHCS). IR
(CCl4): 3 413 ν(E)(NH), 3 373 ν(Z)(NH). 1H NMR: 8.38 s, 1 H (H-10); 7.30–8.25 m , 8 H
(an th racen yl); 4.98 m , 1 H (CH); 3.01 s, 3 H (CH3); 0.97–2.10 m , 11 H (cycloh exyl).
3-(Anthracen-9-yl)-1,1-diethylthiourea (6h ): Yield 87%, m .p. 145–147 °C. For C19H20N2S
(308.5) calculated: 73.99% C, 6.54% H, 9.08% N; foun d: 74.03% C, 6.63% H, 9.23% N. IR
(CHCl3): 3 425 (NH); 1 626, 1 605 (C=C); 1 502, 1 440, 1 142 (NHCS). IR (CCl4): 3 417
ν
(E)(NH), 3 367 ν(Z)(NH). 1H NMR: 8.41 s, 1 H (H-10); 7.30–8.25 m , 8 H (an th racen yl);
7.30 bs, 1 H (NH); 3.90 q, 4 H, J = 7.4 (CH2); 1.39 t, 6 H, J = 7.4 (CH3). 13C NMR: 182.23
(C=S); 128.83, 126.69, 125.43, 123.38 (C-1 to C-8); 131.83 (C-4a, C-10a); 129.50 (C-8a,
C-9a); 130.98 (C-9); 127.09 (C-10); 46.01 (CH2); 13.07 (CH3).
3-(Anthracen-9-yl)-1,1-dipropylthiourea (6i): Yield 85%, m .p. 163–165 °C. For C21H24N2S
(336.5) calculated: 74.96% C, 7.19% H, 8.32% N; foun d: 75.02% C, 7.31% H, 8.41% N. IR
(CHCl3): 3 420 (NH); 1 602 (C=C); 1 500, 1 485, 1 100 (NHCS). IR (CCl4): 3 404 ν(E)(NH),
3 392 ν(Z)(NH). 1H NMR: 8.46 s, 1 H (H-10); 7.37–8.25 m , 8 H (an th racen yl); 7.32 bs, 1 H
(NH); 3.63–3.95 m , 4 H (N-CH2); 1.60–2.20 m , 4 H (CH2); 1.00 t, 6 H, J = 7.4 (CH3).
Preparation of 3-(An th racen -9-yl)th ioureido Am in o Acids 6j–6l.
Gen eral Meth od
Th e followin g m odified procedure was used32: To a solution of th e correspon din g am in o
acid (0.43 m m ol) in water (1.11 m l) wh ich h ad been adjusted to pH 10 with 1 M NaOH, a
solution of 9-isoth iocyan atoan th racen e (5) (70 m g, 0.29 m m ol) in 1,4-dioxan e (3 m l) was
added an d th e m ixture was h eated to 80 °C un till th e en d of th e reaction (TLC, cycloh ex-
an e). Th e reaction m ixture was poured in to water (10 m l) an d 1 M HCl was added dropwise
till a crude product precipitated. Obtain ed com poun ds were filtered off, wash ed with water
an d crystallized from th e m ixture aceton e–dieth yleth er–h eptan e .
[3-(Anthracen-9-yl)thioureido]acetic acid (6j): Yield 80%, m .p. 111–113 °C. For C17H14N2O2S
(310.4) calculated: 65.79% C, 4.55% H, 9.03% N; foun d: 65.83% C, 4.63% H, 9.62% N. IR
(KBr): 3 336 (NH); 1 715 (C=O); 1 620 (C=C); 1 530, 1 435, 1 135 (NHCS). 1H NMR: 9.40 bs,
1 H (NH); 8.66 s, 1 H (H-10); 7.38–8.43 m , 8 H (an th racen yl); 6.75 bs, 1 H (NH); 4.24 s, 2 H
(CH2).
(S)-2-[3-(Anthracen-9-yl)thioureido]propanoic acid (6k ): Yield 72%, m .p. 185–187 °C. For
C
18H16N2O2S (324.4) calculated: 66.65% C, 4.97% H, 8.64% N; foun d: 66.33% C, 5.03% H,
8.72% N. IR (KBr): 3 362, 3 261 (NH); 1 705 (C=O); 1 618 (C=C); 1 522, 1 435, 1 170 (NHCS).
1H NMR: 9.37 bs, 1 H (NH); 8.65 s, 1 H (H-10); 7.25–8.43 m , 8 H (an th racen yl); 6.58 bs, 1 H
(NH); 5.16 m , 1 H (CH); 1.24 d, 3 H (CH3).
(S)-2-[3-(Anthracen-9-yl)thioureido]-3-phenylpropanoic acid (6l): Yield 40%, m .p. 190–193 °C.
For C24H20N2O2S (400.5) calculated: 71.98% C, 5.03% H, 6.99% N; foun d: 72.03% C,
5.23% H, 6.82% N. IR (KBr): 3 365, 3 296 (NH); 1 705 (C=O); 1 620 (C=C); 1 517, 1 435,
1 130 (NHCS). 1H NMR: 9.41 bs,
(an th racen yl); 6.08 bs, 1 H (NH); 5.40 m , 1 H (CH); 2.92 d, 2 H (CH2).
1 H (NH); 8.66 s, 1 H (H-10); 6.50–8.38 m , 8 H
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This study was supported by the Grant Agency for Science of the Slovak Mi
(Registry Number 1/6077/99).
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