Functionalization of the benzo[c][1,2,5]thiadiazole scaffold via Mg-, Zn- and Mn-intermediates

Article abstract of DOI:10.1055/s-0030-1259966

The metalation of all positions of the benzo[c][1,2,5]thiadiazole scaffold using LiCl-solubilized TMP-bases is demonstrated on various substrates. Thus, unsymmetrically substituted benzothiadiazole derivatives and a new fused thiadiazoloindazole have been

Full text of DOI:10.1055/s-0030-1259966

1302
PAPER
Functionalization of the Benzo[c][1,2,5]thiadiazole Scaffold via Mg-, Zn- and
Mn-Intermediates
M
ultifunctiona
i
lizatio
l
n of the
v
Benzo[
c
][1
i
aadiazole ScaffoldZimdars, Heinz Langhals, Paul Knochel*
Department Chemie, Ludwig-Maximilians-Universität München, Butenandtstrasse 5-13, 81377 München, Germany
Fax +49(89)218077680; E-mail: paul.knochel@cup.uni-muenchen.de
Received 28 January 2011; revised 16 February 2011
chloroethane to give the 7-brominated compound (5a) in
Abstract: The metalation of all positions of the benzo[c][1,2,5]thi-
adiazole scaffold using LiCl-solubilized TMP-bases is demonstrat-
ed on various substrates. Thus, unsymmetrically substituted
benzothiadiazole derivatives and a new fused thiadiazoloindazole
have been prepared.
55% yield. Deprotonation of precursor 4d and subsequent
transmetalation with ZnCl2 followed by Negishi cross-
coupling reactions12 with aryl iodides provided the 4,7-
bis-aryl compounds 5b,c in 74 and 84% yield, respective-
ly. Interestingly, all compounds which bear a phenol sub-
unit (4e,f, 5c) display a large Stokes shift of 122 to
123 nm.
Key words: organometallic reagents, metalation, bicyclic com-
pounds, heterocycles, benzo[c][1,2,5]thiadiazole
5,6-Dibromobenzo[c][1,2,5]thiadiazole (6)13 was magne-
siated with TMPMgCl·LiCl14 at –20 °C within 10 minutes
followed by an iodolysis to provide compound 7 in 48%
yield (Scheme 2). Alternatively, a Pd-catalyzed cross-
coupling of 6 with trimethylsilylmethylzinc chloride15
proceeded almost quantitatively to give the benzothiadia-
zole derivative 8 in 92% yield.
Condensed heterocycles gain importance due to their syn-
thetic applications in biological and material science.
Their functionalization is therefore an active research
field.1 The benzothiadiazole scaffold is part of many im-
portant compounds such as the muscle relaxant tizanidine,
which is used for the treatment of chronical migraine and
as antispastic agent.2 Moreover, it is a suitable building
block for semiconducting polymers and copolymers3 as
well as for printable organic semiconductors,4 which find
application as organic thin film transistors (OTFT), organ-
ic photovoltaic cells (OPV), light-emitting diodes (LED),
or as fluorescent probes for bioimaging.5 Despite their
versatile use, only few methods for the functionalization
of this heterocycle have been reported.6,7 4,7-Dibro-
mobenzo[c][1,2,5]thiadiazole (1, Scheme 3)7 has been
used in cross-coupling reactions to provide the corre-
sponding polymers.8 The synthesis of unsymmetrically
functionalized benzo[c][1,2,5]thiadiazoles has also been
published.7,9
Metalation at position 4 of the benzothiadiazole scaffold
could also be achieved by an oxidative magnesium
insertion16 when 4,7-dibromobenzo[c][1,2,5]thiadiazole
(1)7 was used as substrate (Scheme 3). After in situ trans-
metalation with ZnCl2 and a cross-coupling reaction with
MgTMP
E1
E1
N
N
N
N
N
N
N
ii or
iii
i, ii or
i, iv
i
S
S
S
S
N
E2
2
3
4a–i 61–98%
5a: E1 = Ph
5a–c
E2 = Br, 55%
5b: E1 = 4-EtO2CC6H4
E2 = Ph, 74%
5c: E1 = 4-EtO2CC6H4
E2 = 4-MeOC6H4, 84%
Herein, we wish to report a new pathway for the direct ac-
cess to unsymmetrically substituted benzo[c][1,2,5]thia-
diazole derivatives via organometallic intermediates.
Benzo[c][1,2,5]thiadiazole (2)10 was readily magnesiated
at position 4 with TMP2Mg·2LiCl11 at –40 °C to give re-
agent 3 within 14 hours (Scheme 1). After transmetalation
with ZnCl2, the intermediate underwent Pd-mediated
Negishi cross-coupling reactions12 with various aryl ha-
lides and iodothiophenes providing the fluorescent com-
pounds 4a–h in 61–98% yields (Table 1, entries 1–8).
Iodination of 3 gave the corresponding 4-halogenated
compound 4i in 85% yield (entry 9).
Scheme 1 Successive deprotonation and functionalization at posi-
tions 4 and 7. Reagents and conditions: (i) TMP2Mg·2LiCl (1.5 equiv),
THF, –40 °C, 14 h; (ii) ZnCl2 (1.6 equiv), E1I or E2I (1.8 equiv),
Pd(dba)2 (4 mol%), P(o-furyl)3 (8 mol%), 25 °C; (iii) I2 (3.0 equiv),
–40 to 25 °C in 3 h; (iv) (BrCl2C)2 (2.5 equiv), –40 °C, 5 h.
TMS
I
Br
Br
Br
Br
N
N
N
N
N
N
iii
i, ii
S
S
S
Also, a second metalation at position 7 was achieved with
TMP2Mg·2LiCl (Scheme 1). The organometallic reagent
derived from 4c reacted with 1,2-dibromo-1,1,2,2-tetra-
TMS
6
8 92%
7 48%
Scheme 2 Functionalization of 5,6-dibromobenzo[c][1,2,5]thiadia-
zole (6). Reagents and conditions: (i) TMPMgCl·LiCl (1.1 equiv),
THF, –20 °C, 10 min; (ii) I2 (2.0 equiv), to 25 °C in 5 h; (iii)
TMSCH2ZnCl·MgCl2 (4.0 equiv), Pd(OAc)2 (2 mol%), SPhos
(4 mol%), THF, 25 °C, 30 min.
SYNTHESIS 2011, No. 8, pp 1302–1308
Advanced online publication: 24.03.2011
DOI: 10.1055/s-0030-1259966; Art ID: T15911SS
© Georg Thieme Verlag Stuttgart · New York
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x
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Multifunctionalization of the Benzo[c][1,2,5]thiadiazole Scaffold
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Table 1 Functionalization of Benzo[c][1,2,5]thiadiazole (2) via the
Magnesiated Intermediate 3
1) Mg (1.25 equiv)
LiCl (1.25 equiv)
ZnCl2 (1.25 equiv)
THF, 0 °C, 2 h
S
S
N
N
N
N
Entry Electrophile
Time Product
(h)
Yield
(%)a
Br
Br
Br
OMe
2) 4-IC6H4OMe (0.8 equiv)
Pd(dba)2 (2 mol%)
P(o-furyl)3 (4 mol%)
1
9 58%
S
N
N
Scheme 3 Functionalization of 4,7-dibromobenzo[c][1,2,5]thiadia-
zole (1) via magnesium insertion
61b
S
1
2
2-iodothiophene
5
4a
4-iodoanisole, the 4,7-bis-substituted compound 9 was
obtained in 58% yield.
S
S
N
N
N
N
Deprotonation of 1 at position 5 was achieved with
TMP2Mn·2MgCl2·4LiCl.9c The resulting organomanga-
nese reagent reacted with 1,2-dibromo-1,1,2,2-tetrachlo-
roethane to give the 4,5,7-tribromo compound 10 in 70%
yield. This 4,5,7-tribromobenzo[c][1,2,5]thiadiazole was
readily metalated with TMP2Zn·2MgCl2·2LiCl (1.0 equiv,
25 °C, 3 h) and a Cu-catalyzed acylation reaction17 with
3-chlorobenzoyl chloride furnished the tetrasubstituted
benzothiadiazole derivative 12 in 46% yield. The ketone
11 was synthesized according to a reported method,9c and
further reaction with hydrazine gave the fused thiadiazo-
loindazole 13 in 65% yield (Scheme 4).
2,5-diiodothiophene 24
98b,c
S
4b
S
S
S
S
S
S
N
N
N
N
N
N
N
3
4
5
6
7
PhI
3
24
7
83b
72b
74b
82b
63b
4c
N
4-IC6H4CO2Et
4-IC6H4OMe
4-IC6H4OTBS
3-IC6H4CF3
CO2Et
In conclusion, we have prepared a range of new substitut-
ed benzo[c][1,2,5]thiadiazoles using magnesium, zinc,
and manganese intermediates. Further applications of
these polyfunctional N-heterocycles are currently studied
in our laboratories.
4d
N
OMe
4e
Melting points (Mp) were measured on a Büchi B-540 apparatus
and are uncorrected. NMR spectra were recorded of solutions in
CDCl3 on Varian Mercury 200, Bruker AXR 300, Varian VXR
400S and Bruker AMX 600. Chemical shifts are reported as d val-
ues in ppm relative to the residual solvent peak of CHCl3 (dH: 7.25,
dC: 77.0). UV/Vis spectra were recorded on Varian Cary 5000 and
Bruins Omega 20, fluorescence spectra on Varian Cary Eclispe. IR-
spectra were recorded on a Perkin-Elmer Spectrum BX-59343 in-
strument from 4500 to 65 cm–1. For detection, a Smiths detection
DuraSamplIR II Diamond ATR sensor was used. Low-resolution
mass spectra were recorded using a GC/MS-combination from
Hewlett-Packard HP 6890/ MSD 5973. High-resolution mass spec-
tra were recorded on a Finnigan-MAT 95Q instrument (electron
impact ionization, 70 eV). Flash column chromatographic purifica-
tions were carried out using silica gel 60 (0.040–0.063 mesh) from
Merck.
N
7
OTBS
4f
N
CF3
24
4g
N
CF3
CF3
8
9
3,5-(F3C)2C6H3Br 24
61b
Commercially available starting materials with a purity of >97%
were used without further purification. Solvents were distillated and
dried before use.
4h
S
Starting materials 1, 2, 6, and 11 were prepared according to report-
ed methods.
N
N
I2
3
85d
I
4-(Thiophen-2-yl)benzo[c][1,2,5]thiadiazole (4a); Typical Pro-
cedure
4i
In a dry Schlenk tube under an argon atmosphere TMP2Mg·2LiCl
(2.3 mL, 0.6 M in THF, 1.5 mmol) was added dropwise to a solu-
tion of benzo[c][1,2,5]thiadiazole (2; 136 mg, 1.0 mmol) in THF
(1 mL) at –40 °C. After stirring at this temperature for 14 h, a solu-
tion of ZnCl2 (1.6 mL, 1.0 M in THF, 1.6 mmol) was added drop-
wise and the reaction mixture was warmed up to 25 °C. The
resulting solution was treated with Pd(dba)2 (12 mg, 2 mol%,
0.02 mmol), P(o-furyl)3 (9 mg, 4 mol%, 0.04 mmol), and 2-iodo-
a Isolated, analytically pure product.
b Obtained by Pd-catalyzed cross-coupling reaction with Pd(dba)2 (2
mol%) and P(o-furyl)3 (4 mol%) as catalyst and ligand, respectively.
c Obtained by cross-coupling reaction with 0.4 equiv of the electro-
phile.
d Obtained by reaction with I2 (3.0 equiv).
Synthesis 2011, No. 8, 1302–1308 © Thieme Stuttgart · New York

1304
S. Zimdars et al.
PAPER
Br
Br
Br
N
N
S
i
O
Br
Br
Br
Br
Cl
12 46%
E
N
N
N
S
N
1) TMP2Mn⋅2MgCl2⋅4LiCl (0.75 equiv)
S
THF, 0 °C, 3 h
2) E+
ii
N
HN
10 E = Br, 70%
11 E = COPh, 82%
1
Ph
N
N
S
Br
13 65%
Scheme 4 Functionalization of 4,7-dibromobenzo[c][1,2,5]thiadiazole (1). Reagents and conditions: (i) TMP2Zn·2MgCl2·2LiCl (1.0 equiv),
THF, 25 °C, 3 h; CuCN·2LiCl (50 mol%), 3-chlorobenzoyl chloride (1.5 equiv), –15 °C, 3 h; (ii) N2H4·H2O (10.0 equiv), EtOH–CHCl3 (1:1),
60 °C, 10 h.
thiophene (380 mg, 1.8 mmol). After stirring the reaction mixture at
25 °C for 5 h, sat. aq NH4Cl (10 mL) was added, the aqueous layer
was extracted with CH2Cl2 (3 × 30 mL), the combined organic lay-
ers were dried (MgSO4), and the solvent was evaporated in vacuo.
The crude residue was purified by flash chromatography (pentane–
Et3N, 100:1), providing the compound 4a (135 mg, 63%) as a yel-
low solid; mp 53–54 °C.
MS: m/z (%) = 353 (19), 352 (22), 351 (M+, 100), 179 (13), 165
(12), 97 (13), 83 (15), 81 (11), 71 (16), 70 (14), 69 (29), 57 (26), 44
(37).
HRMS: m/z calcd for C16H8N4S3: 351.9911; found: 351.9923.
UV/Vis (CHCl3): lmax (erel) = 434 (1.0), 308 nm (1.8). Fluorescence
(CHCl3): lmax = 532 nm.
IR (ATR): 3071 (w), 2923 (w), 2852 (w), 2752 (w), 1952 (w), 1731
(w), 1591 (w), 1542 (m), 1485 (m), 1428 (w), 1209 (w), 1044 (w),
1036 (w), 851 (m), 841 (m), 820 (m), 802 (s), 751 (s), 707 (m), 684
cm–1 (vs).
1H NMR (300 MHz, CDCl3): d = 8.08 (dd, J = 3.8, 1.1 Hz, 1 H),
7.90 (dd, J = 8.8, 1.1 Hz, 1 H), 7.82 (dd, J = 7.2, 1.1 Hz, 1 H), 7.59
(dd, J = 8.8, 1.1 Hz, 1 H), 7.44 (dd, J = 5.1, 1.1 Hz, 1 H), 7.19 (dd,
J = 5.1, 3.8 Hz, 1 H).
4-Phenylbenzo[c][1,2,5]thiadiazole (4c)
Obtained by the reaction of benzo[c][1,2,5]thiadiazole (2; 136 mg,
1.0 mmol), TMP2Mg·2LiCl (2.3 mL, 0.6 M in THF, 1.5 mmol),
ZnCl2 (1.6 mL, 1.0 M in THF, 1.6 mmol), Pd(dba)2 (12 mg,
2 mol%, 0.02 mmol), P(o-furyl)3 (9 mg, 4 mol%, 0.04 mmol), and
iodobenzene (367 mg, 1.8 mmol) as described above, after purifica-
tion by flash chromatography (pentane–Et2O, 15:1) as a yellow sol-
id; yield: 177 mg (83%); mp 70–71 °C.
13C NMR (75 MHz, CDCl3): d = 155.8, 152.4, 139.5, 129.8, 128.2,
IR (ATR): 3059 (w), 3029 (w), 1540 (w), 1479 (m), 1448 (m), 893
(m), 852 (m), 829 (m), 812 (m), 753 (vs), 696 (s), 670 (m), 636 (m),
625 (m), 608 (m), 596 cm–1 (m).
1H NMR (300 MHz, CDCl3): d = 8.02–7.96 (m, 1 H), 7.93–7.89 (m,
2 H), 7.69–7.64 (m, 2 H), 7.56–7.50 (m, 2 H), 7.47–7.42 (m, 1 H).
13C NMR (75 MHz, CDCl3): d = 155.9, 153.8, 137.6, 134.9, 129.9,
129.5, 128.9, 128.7, 128.0, 120.8.
MS: m/z (%) = 213 (14), 212 (M+, 100), 211 (74), 166 (10), 152 (7),
128.0, 127.9, 127.0, 125.7, 120.3.
MS: m/z (%) = 220 (9), 219 (13), 218 (M+, 100), 217 (10), 185 (5),
174 (9), 173 (10), 109 (5), 87 (5).
HRMS: m/z calcd for C10H6N2S2: 217.9972; found: 217.9964.
UV/Vis (CHCl3): lmax (erel) = 390 (1.0), 308 (1.7), 279 nm (2.5).
Fluorescence (CHCl3): lmax = 492 nm.
2,5-Bis(benzo[c][1,2,5]thiadiazol-4-yl)thiophene (4b)
Obtained by the reaction of benzo[c][1,2,5]thiadiazole (2; 136 mg,
1.0 mmol), TMP2Mg·2LiCl (2.3 mL, 0.6 M in THF, 1.5 mmol),
ZnCl2 (1.6 mL, 1.0 M in THF, 1.6 mmol), Pd(dba)2 (12 mg,
2 mol%, 0.02 mmol), P(o-furyl)3 (9 mg, 4 mol%, 0.04 mmol), and
2,5-diiodothiophene (134 mg, 0.4 mmol) as described above, after
purification by flash chromatography (pentane–Et2O–Et3N,
15:1:0.01) as an orange solid; yield: 140 mg (98%); mp 188–189
°C.
140 (8), 106 (8).
HRMS: m/z calcd for C12H8N2S: 212.0408; found: 212.0409.
UV/Vis (CHCl3): lmax (erel) = 351 (1.0), 315 (1.8), 307 nm (1.8).
Fluorescence (CHCl3): lmax = 449 nm.
Ethyl 4-(Benzo[c][1,2,5]thiadiazol-4-yl)benzoate (4d)
Obtained by the reaction of benzo[c][1,2,5]thiadiazole (2; 136 mg,
1.0 mmol), TMP2Mg·2LiCl (2.3 mL, 0.6 M in THF, 1.5 mmol),
ZnCl2 (1.6 mL, 1.0 M in THF, 1.6 mmol), Pd(dba)2 (12 mg,
2 mol%, 0.02 mmol), P(o-furyl)3 (9 mg, 4 mol%, 0.04 mmol), and
ethyl 4-iodobenzoate (497 mg, 1.8 mmol) as described above, after
purification by flash chromatography (pentane–Et2O–Et3N,
15:1:0.01) as a yellow solid; yield: 205 mg (72%); mp 120–123 °C.
IR (ATR): 2923 (w), 2854 (w), 1651 (w), 1532 (w), 1475 (w), 1363
(w), 1317 (w), 1041 (m), 981 (w), 916 (w), 880 (m), 862 (m), 831
(m), 794 (vs), 752 (m), 739 (s), 694 (m), 632 (w), 620 cm–1 (w).
1H NMR (400 MHz, DMSO-d6): d = 8.25 (s, 2 H), 8.18 (dd, J = 7.1,
0.9 Hz, 2 H), 8.05 (dd, J = 8.7, 0.9 Hz, 2 H), 7.79 (dd, J = 8.7,
7.1 Hz, 2 H).
IR (ATR): 3064 (w), 2989 (w), 1715 (s), 1609 (w), 1480 (w), 1361
(w), 1284 (m), 1271 (s), 1181 (m), 1124 (m), 1098 (m), 1022 (m),
891 (m), 852 (m), 828 (s), 812 (m), 761 (vs), 695 cm–1 (s).
13C NMR (100 MHz, DMSO-d6): d = 155.4, 151.7, 140.5, 130.7,
128.7, 126.7, 126.1, 120.8.
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Multifunctionalization of the Benzo[c][1,2,5]thiadiazole Scaffold
1305
1H NMR (300 MHz, CDCl3): d = 8.21–8.17 (m, 2 H), 8.04–8.00 (m,
3 H), 7.74–7.66 (m, 2 H), 4.42 (q, J = 7.1 Hz, 2 H), 1.42 (t,
J = 7.1 Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 166.6, 155.8, 153.5, 141.9, 133.7,
130.5, 130.0, 129.7, 129.4, 128.4, 121.6, 61.3, 14.6.
2 mol%, 0.02 mmol), P(o-furyl)3 (9 mg, 4 mol%, 0.04 mmol), and
1-iodo-3-(trifluoromethyl)benzene (490 mg, 1.8 mmol) as de-
scribed above, after purification by flash chromatography (pentane–
Et2O–Et3N, 15:1:0.01) as a yellow solid; yield: 175 mg (63%); mp
50–51 °C.
IR (ATR): 1542 (w), 1484 (w), 1441 (w), 1397 (w), 1336 (s), 1314
(m), 1291 (m), 1262 (m), 1172 (m), 1179 (m), 1161 (m), 1106 (vs),
1092 (s), 1072 (s), 964 (m), 896 (m), 832 (m), 797 (s), 752 (s), 732
(m), 700 (s), 667 (m), 654 cm–1 (m).
MS: m/z (%) = 284 (M+, 36), 256 (13), 239 (46), 231 (12), 211 (20),
181 (21), 169 (22), 131 (31), 119 (28), 69 (100).
HRMS: m/z calcd for C15H12N2O2S: 284.0619; found: 284.0605.
1H NMR (300 MHz, CDCl3): d = 8.20–8.17 (br, 1 H), 8.16–8.12
(br, 1 H), 8.07–8.01 (m, 1 H), 7.74–7.61 (m, 4 H).
UV/Vis (CHCl3): lmax (erel) = 348 (1.0), 316 (1.7), 308 (1.7), 271
nm (2.2). Fluorescence (CHCl3): lmax = 438 nm.
13C NMR (75 MHz, CDCl3): d = 155.8, 153.4, 138.3, 133.2, 132.8,
131.3 (q, 2JC,F = 32 Hz), 129.7, 129.3, 128.3, 126.3 (q, 3JC,F = 4 Hz),
125.3 (q, 3JC,F = 4 Hz), 124.4 (q, 1JC,F = 272 Hz), 121.6.
MS: m/z (%) = 282 (6), 281 (16), 280 (M+, 100), 279 (31), 261 (8),
260 (13), 234 (7), 212 (6), 211 (43).
4-(4-Methoxyphenyl)benzo[c][1,2,5]thiadiazole (4e)
Obtained by the reaction of benzo[c][1,2,5]thiadiazole (2; 136 mg,
1.0 mmol), TMP2Mg·2LiCl (2.3 mL, 0.6 M in THF, 1.5 mmol),
ZnCl2 (1.6 mL, 1.0 M in THF, 1.6 mmol), Pd(dba)2 (12 mg,
2 mol%, 0.02 mmol), P(o-furyl)3 (9 mg, 4 mol%, 0.04 mmol), and
4-iodoanisole (421 mg, 1.8 mmol) as described above, after purifi-
cation by flash chromatography (pentane–Et2O, 25:1) as a yellow
solid; yield: 178 mg (74%); mp 126–127 °C.
HRMS: m/z calcd for C13H7F3N2S: 280.0282; found: 280.0267.
UV/Vis (CHCl3): lax (erel) = 343 (1.0), 315 (2.5), 307 nm (2.2). Flu-
orescence (CHCl3, nm): lmax = 435 nm.
IR (ATR): 1601 (w), 1568 (w), 1510 (m), 1479 (m), 1452 (w), 1440
(w), 1277 (m), 1245 (m), 1177 (m), 1023 (s), 896 (m), 856 (m), 833
(m), 804 (vs), 753 (s), 720 (m), 644 (w), 588 cm–1 (m).
1H NMR (300 MHz, CDCl3): d = 7.97–7.86 (m, 3 H), 7.67–7.61 (m,
2 H), 7.09–7.04 (m, 2 H), 3.88 (s, 3 H).
13C NMR (75 MHz, CDCl3): d = 160.1, 155.9, 154.9, 134.4, 130.7,
130.1, 130.0, 127.1, 120.1, 114.3, 55.6.
MS: m/z (%) = 243 (14), 242 (M+, 100), 228 (6), 227 (38), 199 (26),
153 (9).
4-[3,5-Bis(trifluoromethyl)phenyl]benzo[c][1,2,5]thiadiazole
(4h)
Obtained by the reaction of benzo[c][1,2,5]thiadiazole (2; 136 mg,
1.0 mmol), TMP2Mg·2LiCl (2.3 mL, 0.6 M in THF, 1.5 mmol),
ZnCl2 (1.6 mL, 1.0 M in THF, 1.6 mmol), Pd(dba)2 (12 mg,
2 mol%, 0.02 mmol), P(o-furyl)3 (9 mg, 4 mol%, 0.04 mmol) and
1-bromo-3,5-bis(trifluoromethyl)benzene (527 mg, 1.8 mmol) as
described above, after purification by flash chromatography (pen-
tane–Et3N, 100:1) as a yellow solid ; yield: 210 mg (61%); mp 73–
75 °C.
HRMS: m/z calcd for C13H10N2OS: 242.0514; found: 242.0514.
IR (ATR): 3083 (w), 1622 (w), 1544 (w), 1463 (w), 1381 (m), 1352
(w), 1316 (w), 1276 (s), 1183 (m), 1165 (s), 1117 (vs), 1108 (s), 984
(m), 892 (s), 832 (m), 811 (m), 796 (m), 753 (s), 700 (m), 684 (s),
592 cm–1 (w).
1H NMR (300 MHz, CDCl3): d = 8.45–8.41 (br, 2 H), 8.10 (dd,
J = 8.4, 1.6 Hz, 1 H), 7.97–7.93 (s, 1 H), 7.78 (dd, J = 7.1, 1.6 Hz,
1 H), 7.73 (dd, J = 8.4, 7.1 Hz, 1 H).
UV/Vis (CHCl3): lmax (erel) = 373 (1.0), 316 (2.3), 308 (1.9), 303
nm (1.8). Fluorescence (CHCl3): lmax = 495 nm.
4-{4-[(tert-Butyldimethylsilyl)oxy]phenyl}benzo[c][1,2,5]thia-
diazole (4f)
Obtained by the reaction of benzo[c][1,2,5]thiadiazole (2; 136 mg,
1.0 mmol), TMP2Mg⋅2LiCl (2.3 mL, 0.6 M in THF, 1.5 mmol),
ZnCl2 (1.6 mL, 1.0 M in THF, 1.6 mmol), Pd(dba)2 (12 mg,
2 mol%, 0.02 mmol), P(o-furyl)3 (9 mg, 4 mol%, 0.04 mmol), and
tert-butyl(4-iodophenoxy)dimethylsilane (602 mg, 1.8 mmol) as
described above, after purification by flash chromatography (pen-
tane–Et2O–Et3N, 50:1:0.01) as a pale yellow solid; yield: 280 mg
(82%); mp 75–76 °C.
13C NMR (75 MHz, CDCl3): d = 155.7, 153.0, 139.4, 132.2 (q,
3
2JC,F = 32 Hz), 129.6, 129.5 (q, JC,F = 4 Hz), 128.7, 123.6 (q,
1JC,F = 273 Hz), 122.6, 122.2 (sept, 3JC,F = 4 Hz).
MS: m/z (%) = 349 (14), 348 (M+, 100), 347 (21), 329 (16), 328
(22), 327 (5), 302 (10), 280 (5), 279 (40), 163 (5).
IR (ATR): 2953 (w), 2928 (w), 2856 (w), 1603 (m), 1540 (w), 1510
(m), 1483 (m), 1472 (m), 1461 (w), 1280 (s), 1266 (m), 1253 (m),
1176 (m), 1120 (w), 1108 (w), 1105 (w), 919 (s), 833 (s), 803 (vs),
782 (s), 749 (s), 697 (m), 668 cm–1 (m).
HRMS: m/z calcd for C14H6F6N2S: 348.0156; found: 348.0158.
UV/Vis (CHCl3): lmax (erel) = 337 (1.0), 315 (2.4), 308 nm (2.1).
Fluorescence (CHCl3): lmax = 417 nm.
1H NMR (300 MHz, CDCl3): d = 7.96–7.91 (m, 1 H), 7.86–7.81 (m,
2 H), 7.64–7.62 (m, 2 H), 7.01–6.96 (m, 2 H), 1.02 (s, 9 H), 0.26 (s,
6 H).
13C NMR (75 MHz, CDCl3): d = 156.4, 155.9, 153.8, 134.5, 130.6,
129.9, 129.6, 127.2, 120.4, 120.1, 25.9, 18.5, –4.1.
MS: m/z (%) = 343 (18), 342 (M+, 100), 281 (30), 280 (89), 279
(27), 265 (52).
4-Iodobenzo[c][1,2,5]thiadiazole (4i)
In a dry Schlenk tube under an argon atmosphere, TMP2Mg·2LiCl
(2.3 mL, 0.6 M in THF, 1.5 mmol) was added dropwise to a solu-
tion of benzo[c][1,2,5]thiadiazole (2; 136 mg, 1.0 mmol) in THF
(1 mL) at –40 °C. After stirring at this temperature for 14 h, a solu-
tion of I2 (3 mL, 1.0 M in THF, 3.0 mmol) was added dropwise and
the reaction mixture was warmed up to 25 °C within 3 h. Sat. aq
NH4Cl (10 mL) and sat. aq Na2S2O3 (3 mL) were added, the aque-
ous layer was extracted with CH2Cl2 (3 × 30 mL), the combined or-
ganic layers were dried (MgSO4), and the solvent was evaporated in
vacuo. The crude residue was purified by flash chromatography
(pentane) and the compound 4i was obtained as a yellow solid;
yield: 220 mg (85%).
HRMS: m/z calcd for C18H22N2OSSi: 342.1222; found: 342.1228.
UV/Vis (CHCl3): lmax (erel) = 371 (1.0), 316 (2.2), 308 (1.9), 303
nm (1.8). Fluorescence (CHCl3): lmax = 493 nm.
4-(3-(Trifluoromethyl)phenyl)benzo[c][1,2,5]thiadiazole (4g)
Obtained by the reaction of benzo[c][1,2,5]thiadiazole (2; 136 mg,
1.0 mmol), TMP2Mg·2LiCl (2.3 mL, 0.6 M in THF, 1.5 mmol),
ZnCl2 (1.6 mL, 1.0 M in THF, 1.6 mmol), Pd(dba)2 (12 mg,
1H NMR corresponded to that of the commercially available com-
pound from Maybridge.
Synthesis 2011, No. 8, 1302–1308 © Thieme Stuttgart · New York

1306
S. Zimdars et al.
PAPER
HRMS: m/z calcd for C21H16N2O2S: 360.0932; found: 360.0925.
1H NMR (300 MHz, CDCl3): d = 8.10 (dd, J = 7.1, 0.9 Hz, 1 H),
7.97 (dd, J = 8.7, 1.0 Hz, 1 H), 7.34 (dd, J = 8.8, 7.1 Hz, 1 H).
13C NMR (75 MHz, CDCl3): d = 155.7, 152.9, 139.0, 130.5, 121.7,
87.2.
UV/Vis (CHCl3): lmax (erel) = 379 (1.0), 318 (1.1), 286 nm (2.2).
Fluorescence (CHCl3): lmax = 481 nm.
Ethyl 4-[7-(4-Methoxyphenyl)benzo[c][1,2,5]thiadiazol-4-
yl]benzoate (5c)
HRMS: m/z calcd for C6H3IN2S: 261.9062; found: 261.9069.
Obtained by the reaction of ethyl 4-(benzo[c][1,2,5]thiadiazol-4-
yl)benzoate (4d; 284 mg, 1.0 mmol), TMP2Mg⋅2LiCl (2.3 mL,
0.6 M in THF, 1.5 mmol), ZnCl2 (1.6 mL, 1.0 M in THF, 1.6 mmol),
Pd(dba)2 (12 mg, 2 mol%, 0.02 mmol), P(o-furyl)3 (9 mg, 4 mol%,
0.04 mmol), and 4-iodoanisole (421 mg, 1.8 mmol) as described
above, after purification by flash chromatography (pentane–Et2O,
gradient: 5:1, 3:1, 1:1) as an orange solid; yield: 325 mg (84%); mp
149 °C (dec.).
4-Bromo-7-phenylbenzo[c][1,2,5]thiadiazole (5a)
In a dry Schlenk tube under an argon atmosphere TMP2Mg·2LiCl
(2.3 mL, 0.6 M in THF, 1.5 mmol) was added dropwise to a solu-
tion of 4-phenylbenzo[c][1,2,5]thiadiazole (4c; 212 mg, 1.0 mmol)
in THF (2 mL) at –40 °C. After stirring at this temperature for 14 h,
(BrCl2C)2 (2.5 mL, 1.0 M in THF, 2.5 mmol) was added dropwise
and the reaction mixture was stirred at –40 °C for 5 h. Sat. aq NH4Cl
(10 mL) was added, the aqueous layer was extracted with CH2Cl2
(3 × 30 mL), the combined organic layers were dried (MgSO4), and
the solvent was evaporated in vacuo. The crude residue was purified
by flash chromatography (pentane– Et3N, 100:1), providing the
compound 5a (160 mg, 55%) as a beige solid; mp 84–85 °C.
IR (ATR): 3039 (w), 2980 (w), 1868 (w), 1708 (s), 1607 (m), 1572
(w), 1552 (w), 1504 (m), 1483 (m), 1285 (s), 1255 (s), 1174 (m),
1129 (m), 1106 (s), 1022 (s), 884 (m), 848 (m), 816 (vs), 766 (s),
699 (s), 590 cm–1 (m).
IR (ATR): 3052 (w), 3031 (w), 1568 (w), 1524 (w), 1475 (m), 1447
(m), 1326 (w), 1188 (w), 1144 (w), 1073 (w), 932 (m), 884 (m), 848
(m), 835 (m), 753 (s), 692 (vs), 669 (m), 632 (m), 615 (m), 609
cm–1 (m).
1H NMR (400 MHz, toluene-d8): d = 8.05–8.02 (m, 2 H), 7.71–7.68
(m, 4 H), 7.11 (d, J = 7.3 Hz, 1 H), 7.08 (d, J = 7.3 Hz, 1 H), 6.69–
6.65 (m, 2 H), 3.93 (q, J = 7.0 Hz, 2 H), 3.14 (s, 3 H), 0.86 (t,
J = 7.0 Hz, 3 H).
1H NMR (300 MHz, CDCl3): d = 7.93–7.85 (m, 3 H), 7.58–7.43 (m,
13C NMR (100 MHz, toluene-d8): d = 165.6, 160.2, 154.1, 153.9,
141.6, 133.6, 131.0, 130.6, 130.2, 129.7, 129.6, 129.1, 128.2, 126.5,
113.9, 60.4, 54.4, 14.0.
4 H).
13C NMR (75 MHz, CDCl3): d = 154.1, 153.4, 136.9, 134.3, 132.5,
129.4, 129.0, 128.5, 113.4.
MS: m/z (%) = 392 (7), 391 (22), 390 (M+, 100), 375 (6), 362 (10),
347 (7), 345 (11), 274 (6), 172 (7), 137 (5).
MS: m/z (%) = 292 (90), 291 (39), 290 (M+, 100), 289 (21), 278
(20), 212 (18), 211 (85), 210 (21), 179 (16), 178 (17), 140 (22), 106
(29).
HRMS: m/z calcd for C22H18N2O3S: 390.1038; found: 390.1039.
UV/Vis (CHCl3): lmax (erel) = 398 (1.0), 294 nm (2.2). Fluorescence
(CHCl3): lmax = 522 nm.
HRMS: m/z calcd for C12H7BrN2S: 289.9513; found: 289.9505.
UV/Vis (CHCl3): lmax (erel) = 370 (1.0), 316 (1.8), 308 (1.5), 303
nm (1.5). Fluorescence (CHCl3): lmax = 470 nm.
5,6-Dibromo-4-iodobenzo[c][1,2,5]thiadiazole (7)
In a dry Schlenk tube under an argon atmosphere TMPMgCl⋅LiCl
(1.0 mL, 1.1 M in THF, 1.1 mmol) was added dropwise to a solu-
tion of 5,6-dibromobenzo[c][1,2,5]thiadiazole (6; 294 mg,
1.0 mmol) in THF (4 mL) at –20 °C. After stirring at this tempera-
ture for 10 min, I2 (2.0 mL, 1.0 M in THF, 2.0 mmol) was added
dropwise and the reaction mixture was slowly warmed up to 25 °C
in 5 h. Sat. aq NH4Cl (10 mL) and sat. aq Na2S2O3 (5 mL) were add-
ed, the aqueous layer was extracted with CH2Cl2 (3 × 30 mL), the
combined organic layers were dried (MgSO4), and the solvent was
evaporated in vacuo. The crude residue was purified by flash chro-
matography (pentane–Et2O, 200:1), providing the compound 7
(200 mg, 48%) as a yellow solid; mp 171–172 °C.
Ethyl 4-(7-Phenylbenzo[c][1,2,5]thiadiazol-4-yl)benzoate (5b)
In a dry Schlenk tube under an argon atmosphere TMP2Mg·2LiCl
(2.3 mL, 0.6 M in THF, 1.5 mmol) was added dropwise to a solu-
tion of ethyl 4-(benzo[c][1,2,5]thiadiazol-4-yl)benzoate (4d;
284 mg, 1.0 mmol) in THF (5 mL) at –40 °C. After stirring at this
temperature for 14 h, ZnCl2 (1.6 mL, 1.0 M in THF, 1.6 mmol) was
added dropwise and the reaction mixture was warmed up to 25 °C.
The resulting solution was treated with Pd(dba)2 (12 mg, 2 mol%,
0.02 mmol), P(o-furyl)3 (9 mg, 4 mol%, 0.04 mmol), and iodoben-
zene (370 mg, 1.8 mmol). After stirring the reaction mixture at
25 °C for 7 h, sat. aq NH4Cl (10 mL) was added, the aqueous layer
was extracted with CH2Cl2 (3 × 30 mL), the combined organic lay-
ers were dried (MgSO4), and the solvent was evaporated in vacuo.
The crude residue was purified by flash chromatography (pentane–
Et2O–Et3N, 100:1:0.01), providing the compound 5b (270 mg,
74%) as a yellow solid; mp 139–142 °C.
IR (ATR): 3066 (vw), 2922 (w), 2852 (vw), 1712 (w), 1560 (w),
1472 (m), 1418 (m), 1368 (w), 1330 (w), 1296 (w), 1244 (w), 1230
(s), 1176 (w), 1160 (w), 1118 (w), 1104 (m), 1096 (m), 964 (w), 952
(m), 908 (m), 876 (m), 856 (vs), 840 (s), 758 (w), 734 (w), 718 (m),
682 (w), 622 cm–1 (w).
IR (ATR): 2972 (w), 1700 (s), 1607 (m), 1552 (w), 1472 (w), 1451
(w), 1411 (w), 1368 (w), 1277 (s), 1181 (m), 1128 (m), 1104 (m),
1080 (w), 1017 (m), 973 (w), 932 (w), 890 (m), 846 (s), 772 (s), 764
(vs), 696 (s), 616 cm–1 (m).
1H NMR (300 MHz, CDCl3): d = 8.23–8.19 (m, 2 H), 8.07–8.03 (m,
2 H), 7.97–7.93 (m, 2 H), 7.84 (d, J = 7.3 Hz, 1 H), 7.79 (d,
J = 7.3 Hz, 1 H), 7.58–7.52 (m, 2 H), 7.49–7.44 (m, 1 H), 4.43 (q,
J = 7.1 Hz, 2 H), 1.43 (t, J = 7.1 Hz, 3 H).
1H NMR (300 MHz, CDCl3): d = 8.38 (s, 1 H).
13C NMR (75 MHz, CDCl3): d = 156.2, 150.7, 135.5, 126.2, 124.6,
95.8.
MS: m/z (%) = 422 (56), 420 (100), 418 (53), 214 (25), 212 (23),
133 (19), 128 (42), 127 (33), 80 (20), 43 (22).
HRMS: m/z calcd for C6HBr2IN2S: 417.7272; found: 417.7274.
5,6-Bis((trimethylsilyl)methyl)benzo[c][1,2,5]thiadiazole (8)
In a dry Schlenk tube under an argon atmosphere TMSCH2MgCl
(3.39 mL, 1.18 M in Et2O, 4.0 mmol) was added dropwise to anhyd
ZnCl2 (550 mg, 4.0 mmol) in THF (4 mL) at 0 °C and the mixture
was warmed up to 25 °C. 5,6-dibromobenzo[c][1,2,5]thiadiazole
(6; 294 mg, 1.0 mmol), Pd(OAc)2 (5 mg, 2 mol%, 0.02 mmol), and
SPhos (16 mg, 4 mol%, 0.04 mmol) were successively added. After
13C NMR (75 MHz, CDCl3): d = 166.6, 154.4, 154.1, 141.9, 137.5,
134.5, 132.4, 130.4, 131.1, 129.5, 129.4, 128.9, 128.9, 128.8, 128.2,
61.3, 14.6.
MS: m/z (%) = 362 (7), 361 (21), 360 (M+, 100), 332 (14), 316 (10),
315 (46), 288 (4), 287 (16), 286 (6), 255 (9), 254 (4), 157 (6).
Synthesis 2011, No. 8, 1302–1308 © Thieme Stuttgart · New York

PAPER
Multifunctionalization of the Benzo[c][1,2,5]thiadiazole Scaffold
1H NMR (300 MHz, CDCl3): d = 8.08 (s, 1 H).
1307
stirring for 30 min, sat aq NH4Cl (10 mL) was added, the aqueous
layer was extracted with CH2Cl2 (3 × 30 mL), the combined organic
layers were dried (MgSO4), and the solvent was evaporated in vac-
uo. The crude residue was purified by flash chromatography (pen-
tane–Et2O, 100:1), providing the compound 8 (283 mg, 92%) as a
colorless solid; mp 90–91 °C.
13C NMR (75 MHz, CDCl3): d = 153.5, 153.0, 135.9, 127.1, 116.6,
113.7.
MS: m/z (%) = 376 (32), 374 (100), 372 (97), 370 (30), 295 (15),
293 (29), 291 (14), 216 (18), 214 (19), 58 (24), 43 (67).
HRMS: m/z calcd for C6HBr3N2S: 369.7411; found: 369.7413.
IR (ATR): 2954 (w), 2898 (vw), 1492 (w), 1458 (w), 1420 (w),
1400 (w), 1268 (w), 1246 (m), 1160 (w), 1140 (m), 1084 (w), 886
(w), 868 (m), 834 (vs), 820 (s), 778 (m), 758 (w), 712 (w), 694 (m),
664 cm–1 (w).
1H NMR (300 MHz, CDCl3): d = 7.53 (s, 2 H), 2.24 (s, 4 H), 0.04
(s, 18 H).
(3-Chlorophenyl)(4,6,7-tribromobenzo[c][1,2,5]thiadiazol-5-
yl)methanone (12)
In
a
dry Schlenk tube under an argon atmosphere
TMP2Zn⋅2MgCl2⋅2LiCl (2.0 mL, 0.5 M in THF, 1.0 mmol) was
added dropwise to a solution of 4,6,7-tribromobenzo[c][1,2,5]thia-
diazole (10; 373 mg, 1.0 mmol) in THF (1 mL). After stirring for
3 h, CuCN⋅2LiCl (0.5 mL, 1.0 M in THF, 50 mol%, 0.5 mmol) and
3-chlorobenzoyl chloride (263 mg, 1.5 mmol) were successively
added at –15 °C, and the reaction mixture stirred for 3 h. Sat. aq
NH4Cl (20 mL) and NH3 (5 mL) were added, the aqueous layer was
extracted with CH2Cl2 (3 × 40 mL), the combined organic layers
were dried (MgSO4), and the solvent was evaporated in vacuo. The
crude residue was purified by flash chromatography (pentane–Et2O,
20:1), providing the compound 12 (233 mg, 46%) as a yellow solid;
mp 195–198 °C.
13C NMR (75 MHz, CDCl3): d = 153.6, 142.7, 117.7, 25.5, –1.4.
MS: m/z (%) = 308 (11), 295 (6), 294 (11), 291 (43), 74 (9), 73
(100), 45 (17), 43 (12).
HRMS: m/z calcd for C14H24N2SSi2: 308.1199; found: 308.1192.
4-Bromo-7-(4-methoxyphenyl)benzo[c][1,2,5]thiadiazole (9)
In a dry Schlenk tube under an argon atmosphere LiCl (106 mg,
2.5 mmol), Mg (61 mg, 2.5 mmol), ZnCl2 (2.5 mL, 1.0 M in THF,
2.5 mmol), and THF (5 mL) were successively added. At 0 °C, 4,7-
dibromobenzo[c][1,2,5]thiadiazole (1; 588 mg, 2.0 mmol) was add-
ed and the reaction mixture stirred for 2 h. The resulting brown so-
lution was canulated to a mixture of Pd(dba)2 (30 mg, 2 mol%,
0.04 mmol), P(o-furyl)3 (16 mg, 4 mol%, 0.08 mmol), and 4-io-
doanisole (374 mg, 1.6 mmol) in THF (2 mL). After stirring at
25 °C for 5 h, sat. aq NH4Cl (20 mL) was added, the aqueous layer
was extracted with CH2Cl2 (3 × 40 mL), the combined organic lay-
ers were dried (MgSO4), and the solvent was evaporated in vacuo.
The crude residue was purified by flash chromatography (pentane–
Et2O, 50:1), providing the compound 9 (300 mg, 58%) as a yellow
solid; mp 133–136 °C.
IR (ATR): 3096 (w), 3072 (w), 2930 (w), 2872 (w), 1748 (w), 1722
(m), 1680 (s), 1644 (m), 1622 (m), 1588 (m), 1570 (m), 1466 (w),
1448 (m), 1422 (m), 1380 (m), 1370 (m), 1346 (w), 1278 (m), 1264
(vs), 1246 (vs), 1188 (s), 1172 (s), 1132 (s), 1074 (m), 1052 (m),
1000 (w), 968 (w), 942 (w), 908 (m), 884 (s), 846 (w), 810 (m), 788
(m), 758 (s), 738 (vs), 720 (s), 672 (s), 604 cm–1 (w).
1H NMR (300 MHz, CDCl3): d = 7.89–7.88 (m, 1 H), 7.74–7.71 (m,
1 H), 7.66–7.63 (m, 1 H), 7.49–7.46 (m, 1 H).
13C NMR (75 MHz, CDCl3): d = 190.7, 153.1, 151.4, 141.8, 135.7,
135.6, 134.7, 130.6, 129.5, 129.4, 128.0, 123.8, 118.8, 111.3.
IR (ATR): 3048 (vw), 2990 (vw), 2934 (vw), 2896 (vw), 2836 (vw),
1896 (vw), 1608 (m), 1530 (w), 1508 (m), 1482 (m), 1462 (w), 1454
(w), 1438 (w), 1342 (vw), 1308 (w), 1282 (m), 1272 (w), 1248 (s),
1180 (s), 1152 (w), 1116 (w), 1084 (w), 1030 (s), 972 (vw), 942 (w),
930 (w), 880 (s), 838 (m), 826 (vs), 796 (m), 732 (w), 654 (vw), 628
cm–1 (vw).
1H NMR (300 MHz, CDCl3): d = 7.91–7.84 (m, 3 H), 7.52 (d,
J = 7.5 Hz, 1 H), 7.09–7.04 (m, 2 H), 3.90 (s, 3 H).
13C NMR (75 MHz, CDCl3): d = 160.1, 153.9, 153.2, 133.6, 132.3,
130.3, 129.0, 127.4, 114.1, 112.2, 55.4.
MS: m/z (%) = 510 (28), 433 (55), 431 (78), 429 (33), 401 (16), 399
(16), 141 (31), 139 (100), 111 (65), 75 (35).
HRMS: m/z calcd for C13H4Br3ClN2OS: 507.7283; found:
507.7275.
4-Bromo-6-phenyl-8H-[1,2,5]thiadiazolo[3,4-g]indazole (13)
In a 50 mL round-bottom flask, N2H4⋅H2O (0.5 g, 10.0 mmol) was
added dropwise to a solution of (4,7-dibromobenzo[c][1,2,5]thiadi-
azol-5-yl)(phenyl)methanone (11; 398 mg, 1.0 mmol) in EtOH–
CHCl3 (6 mL each). The reaction mixture was stirred at 60 °C for
10 h, the solvent was evaporated in vacuo and the crude residue was
purified by flash chromatography (isohexane–EtOAc, gradient: 5:1,
3:1), providing the compound 13 (214 mg, 65%) as a yellow solid;
mp 270–272 °C.
MS: m/z (%) = 323 (16), 322 (100), 321 (15), 320 (98), 307 (35),
305 (35), 279 (20), 277 (21), 198 (26).
HRMS: m/z calcd for C13H9BrN2OS: 319.9619; found: 319.9615.
IR (ATR): 3264 (m), 1746 (vw), 1610 (vw), 1516 (vw), 1496 (w),
1446 (w), 1396 (w), 1362 (m), 1338 (w), 1274 (vw), 1246 (w), 1230
(w), 1140 (vw), 1112 (w), 1104 (w), 1074 (w), 978 (w), 888 (m),
870 (vs), 838 (m), 764 (w), 718 (s), 694 (s), 674 (m), 634 cm–1 (w).
1H NMR (400 MHz, DMSO-d6): d = 8.47 (m, 1 H), 7.99–7.90 (m,
2 H), 7.63–7.45 (m, 3 H).
4,5,7-Tribromobenzo[c][1,2,5]thiadiazole (10)
In
a
dry Schlenk tube under an argon atmosphere
TMP2Mn⋅2MgCl2⋅4LiCl (7.5 mL, 0.5 M in THF, 3.75 mmol) was
added dropwise to a solution of 4,7-dibromobenzo[c][1,2,5]thiadia-
zole (1; 1.47 g, 5.0 mmol) in THF (5 mL) at 0 °C. After stirring at
this temperature for 3 h, (BrCl2C)2 (7.5 mL, 1.0 M in THF,
7.5 mmol) was added dropwise and the reaction mixture was slowly
warmed up to 25 °C in 5 h. Sat. aq NH4Cl (20 mL) was added, the
aqueous layer was extracted with CH2Cl2 (3 × 40 mL), the com-
bined organic layers were dried (MgSO4), and the solvent was evap-
orated in vacuo. The crude residue was purified by flash
chromatography (pentane–Et2O, 100:1), providing the compound
10 (1.3 g, 70%) as a yellow solid; mp 153–154 °C.
MS: m/z (%) = 333 (16), 332 (100), 331 (20), 330 (92), 329 (5), 218
(9), 164 (5), 77 (15).
HRMS: m/z calcd for C13H7BrN4S: 329.9575; found: 329.9566.
Acknowledgment
The research leading to these results has received funding from the
European Research Council under the European Community’s
Seventh Framework Programme (FP7/2007-2013) ERC grant
agreement No. 227763. We are grateful to W. C. Heraeus GmbH
and Chemetall GmbH (Frankfurt) for generous gifts of chemicals.
IR (ATR): 1736 (vw), 1570 (w), 1540 (vw), 1508 (vw), 1488 (w),
1478 (w), 1452 (w), 1368 (vw), 1302 (w), 1294 (w), 1260 (vw),
1222 (m), 1184 (w), 1138 (w), 1124 (w), 972 (m), 940 (w), 878 (vs),
864 (m), 844 (m), 750 (w), 690 cm–1 (w).
Synthesis 2011, No. 8, 1302–1308 © Thieme Stuttgart · New York

1308
S. Zimdars et al.
PAPER
(9) (a) Bijleveld, J. C.; Shahid, M.; Gilot, J.; Wienk, M. M.;
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