PAPER
Photocrosslinking with 1,2,3-Thiadiazole
2543
4-(Allyloxy)acetophenone 4-Toluenesulfonylhydrazone (17)
Ketone 15 (3.0 g, 17.0 mmol) was added to a boiling solution of
TsNHNH2 (16, 3.17 g, 17.02 mmol) in EtOH (15 mL). The mixture
was refluxed for 1 h and then concentrated till the product started to
precipitate. Recrystallization (EtOH) gave 17 (5.3 g, 91%) as a col-
orless powder; mp 138 °C.
4-[4-(Oxiran-2-ylmethoxy)phenyl]-1,2,3-thiadiazole (1d) by
Epoxidation of 1b
MCPBA (18, 0.78 g, 4.52 mmol) dissolved in anhyd CH2Cl2 (9 mL)
was added dropwise to a soln of 1b (0.70 g, 3.21 mmol) in anhyd
CH2Cl2 (10 mL) at 0 °C. The mixture was stirred vigorously at r.t.
for 6 h and at reflux for 3 h. The mixture was filtered and the soln
was washed with 10% NaOH (3 × 10 mL) and H2O (2 × 20 mL).
The dried (MgSO4) and concentrated solution was chromato-
graphed (silica gel, 3 × 80 cm, EtOH–CH2Cl2, 1:40). The first frac-
tion consisted of unreacted 1b and the second fraction of the product
1d (0.30 g, 36%); colorless crystals; mp 77–78 °C.
1H NMR (CDCl3): d = 2.11 (s, 3 H, CH3), 2.38 (s, 3 H, CH3), 4.50–
4.55 (m, 2 H, CH2), 5.25–5.29 (m, 3Jcis = 10.0 Hz, 1 H, =CH2), 5.38–
3
5.43 (m, Jtrans = 17.0 Hz, 1 H, =CH2), 5.98–6.03 (m, 1 H, =CH),
6.82/7.90 (AA¢BB¢, 4 H, Harom), 7.28/7.55 (AA¢BB¢, 4 H, Harom),
7.94 (s, 1 H, NH).
1H NMR (CDCl3): d = 2.75–2.79/2.90–2.95/3.35–3.39 (3 m, 3 H,
oxirane ring), 3.95–3.99/4.26–4.30 (2 m, 2 H, OCH2), 7.04/7.93
(AA¢BB¢, 4 H, benzene ring), 8.52 (s, 1 H, H5).
13C NMR (CDCl3): d = 13.2, 21.5 (CH3), 68.8 (OCH2), 114.4,
127.7, 128.1, 129.5 (CHarom), 117.8 (=CH2), 132.9 (=CH), 130.1,
135.6, 144.0, 159.8 (arom Cq), 152.6 (CN).
13C NMR (CDCl3): d = 44.5 (CH2, oxirane ring), 50.0 (CH, oxirane
ring), 68.9 (OCH2), 115.3, 128.8 (CHPh), 124.1, 159.4 (Cq-Ph),
128.5 (C5), 162.5 (C4).
MS (FD): m/z (%) = 344 (100) [M+].
Anal. Calcd for C18H20N2O3S (344.4): C, 62.77; H, 5.85; N, 8.13.
Found: C, 62.47; H, 5.82; N, 8.12.
MS (FD): m/z (%) = 234 (100) [M+].
4-[4-(Allyloxy)phenyl]-1,2,3-thiadiazole (1b); Typical Proce-
dure
Anal. Calcd for C11H10N2O2S: C, 56.40; H, 4.30; N, 11.96; S, 13.69.
Found: C, 56.63; H, 4.23; N, 11.93; S, 13.71.
Hydrazone 17 (2.0 g, 5.81 mmol) was added portionwise at r.t. to
freshly distilled SOCl2 (8.0 mL, 13.1 g, 110 mmol). The vigorously
stirred mixture started immediately to react. The temperature was
kept at 10–15 °C by cooling in an ice bath and stirred for 1 h and
this was continued at r.t. for 6 h. The excess SOCl2 was removed (1
kPa) and the residue purified by column chromatography (silica gel,
5 × 100 cm, toluene). After the first fraction of TsCl, 1b (1.1 g, 90%)
was obtained as a colorless powder; mp 74 °C.
4-Hydroxyacetophenone 4-Toluenesulfonylhydrazone (19)
4-Hydroxyacetophenone (13, 2.19 g, 16.0 mmol) was added to a hot
soln of TsNHNH2 (16, 3.0 g, 16.0 mmol) in EtOH (16 mL). The
mixture was refluxed for 1 h then concentrated till the product start-
ed to precipitate. The obtained yellowish powder was washed (cold
EtOH) and recrystallized (EtOH); yield: 4.8 g (99%); mp 93–94 °C.
1H NMR (DMSO-d6): d = 2.12 (s, 3 H, CH3), 2.36 (s, 3 H, CH3),
6.77/7.83 (AA¢BB¢, 4 H, Harom), 7.42/7.51 (AA¢BB¢, 4 H, Harom),
9.79 (s, 1 H, NH), 10.29 (s, 1 H, OH).
1H NMR (CDCl3): d = 4.58–4.63 (m, 2 H, CH2), 5.25–5.30 (m,
3
3Jcis = 10.0 Hz, 1 H, =CH2), 5.45–5.49 (m, Jtrans = 16.0 Hz, 1 H,
=CH2), 6.03–6.08 (m, 1 H, =CH), 7.00/7.93 (AA¢BB¢, 4 H, Harom),
8.50 (s, 1 H, H5).
13C NMR (DMSO-d6): d = 14.0, 20.9 (CH3), 115.0, 127.4, 127.5,
129.3 (CHarom), 128.3, 136.3, 143.1 (arom Cq), 153.4 (CN), 158.7
(arom CqO).
13C NMR (CDCl3): d = 68.8 (OCH2), 115.3, 128.7 (CHarom), 117.9
(=CH2), 132.9 (=CH), 128.4 (C5), 123.6, 159.5 (arom Cq), 162.6
(C4).
MS (EI): m/z (%) = 304 (13) [M+], 149 (100), 119 (55), 92 (53).
Anal. Calcd for C15H16N2O3S (304.4): C, 59.19; H, 5.30; N, 9.20.
Found: C, 59.22; H, 5.31; N, 9.18.
MS (FD): m/z (%) = 218 (100) [M+].
HRMS: m/z [M+] calcd for C11H10N2OS: 218.0514; found:
218.0518.
4-(1,2,3-Thiadiazol-4-yl)phenol (1e)
Following the typical procedure for 1b using 19 (3.0 g, 9.87 mmol)
yielded 1e (1.3 g, 76%) as an ochre powder; mp 166 °C. The product
was identified by comparison with an authentic sample.36,37
(Z/E)-4-[4-(Prop-2-enyloxy)phenyl]-1,2,3-thiadiazole [(E/Z)-1c]
DABCO (0.69 g, 6.37 mmol), RhCl(PPh3)3 (0.5 g, 0.54 mmol), and
1b (1.14 g, 5.20 mmol) were added to a mixture of EtOH (220 mL),
toluene (80 mL), and H2O (30 mL). The reaction was performed at
85 °C under an N2 atmosphere [monitored by TLC (silica gel, tolu-
ene)]. After 30 h the volatile parts were evaporated (1.0 kPa) and the
residue purified by column chromatography (silica gel, 3 × 100 cm,
CH2Cl2–EtOH, 25:1); 1c (0.70 g, 64%) was the first fraction; color-
less crystals; mp 81–82 °C; ratio Z/E 56:44 (1H NMR). Later frac-
tions consist of starting compound 1b and some 4-(1,2,3-thiadiazol-
4-yl)phenol (1e), which was formed by ether cleavage.
1H NMR (DMSO-d6): d = 6.95/7.97 (AA¢BB¢, 4 H, Harom), 8.97 (s,
1 H, OH), 9.39 (s, 1 H, 5-H).
13C NMR (DMSO-d6): d = 116.0, 128.7 (CHarom), 121.8, 158.6
(arom Cq), 130.7 (C5).
4-[4-(Oxiran-2-ylmethoxy)phenyl]-1,2,3-thiadiazole (1d) by
Reaction of 1e with ( )-Epichlorohydrin (20)
A mixture of thiadiazole 1e (0.23 g, 1.29 mmol), ( )-2-(chloro-
methyl)oxirane (20, 0.23 g, 2.49 mmol), K2CO3 (O.30 g, 2.16
mmol), and KI (0.30 g, 1.81 mmol) in anhyd acetone (30 mL) was
refluxed for 30 h. The mixture was treated with H2O (20 mL) and
extracted with CH2Cl2 (3 × 25 mL). The dried (MgSO4) organic
phase was evaporated and the residue purified by column chroma-
tography (silica gel, 4 × 70 cm, CH2Cl2–EtOH, 20:1) to give 1d as
colorless crystals; yield: 0.20 g (63%); mp 77–78 °C.
1H NMR (CDCl3): d [(E)-1c] = 1.65–1.69 (m, 3 H, CH3), 5.41–5.46
3
3
(m, J = 15.0 Hz, 1 H, =CH), 6.43–6.48 (m, J = 15.0 Hz, 1 H,
=CH), 7.06/7.96 (AA¢BB¢, 4 H, Harom), 8.53 (s, 1 H, H5);
d [(Z)-1c] = 1.70–1.74 (m, 3 H, CH3), 4.92–4.97 (m, 3J = 8.0 Hz, 1
H, =CH), 6.40–6.45 (m, 3J = 8.0 Hz, 1 H, =CH), 7.09/7.98
(AA¢BB¢, 4 H, Harom), 8.53 (s, 1 H, H5).
13C NMR (CDCl3): d [(E)-1c] = 12.2 (CH3), 109.5, 141.1 (=CH),
116.7, 128.8 (CHarom), 125.1, 158.4 (arom Cq), 128.8 (C5), 162.5
(C4).
4-(3-Bromopropoxy)acetophenone (22)
1,3-Dibromopropane (21, 30.0 g, 148.6 mmol), ketone 13 (2.0 g,
14.9 mmol), and K2CO3 (20.0 g, 145.0 mmol) in anhyd acetone (80
mL) were refluxed for 40 h. The filtered mixture was evaporated (1
kPa); the solvent and excess 21 distilled off. The residue was puri-
fied by column chromatography [silica gel, 5 × 100 cm, petroleum
MS (FD): m/z (%) = 218 (24) [M+], 190 (87), 158 (32), 148 (100),
77 (41).
Anal. Calcd for C11H10N2OS (218.3): C, 60.53; H, 4.62; N, 12.83.
Found: C, 60.62; H, 4.65; N, 12.81.
Synthesis 2009, No. 15, 2539–2546 © Thieme Stuttgart · New York