Notes
J . Org. Chem., Vol. 66, No. 23, 2001 7929
and the residue was triturated with water (100 mL). The
suspension was acidified with 10% aq HCl to pH 1 and stirred
for 2 h at room temperature. The precipitate was filtered off,
washed with water (200 mL), and dried under reduced pressure
(1 mmHg, P2O5, 24 h) to afford the title compound 8 as a white
solid (1.30 g, 85%): 1H NMR (DMSO-d6) δ 0.84 (t, J ) 6.7 Hz,
3H), 1.17-1.46 (m, 18H), 1.74 (quint, J ) 6.8 Hz, 2H), 4.16 (t, J
) 6.5 Hz, 2H), 7.38 (s, 1H), 7.89 (d, J ) 8.5 Hz, 2H), 8.00 (d, J
) 8.5 Hz, 2H), the carboxylic acid signal was not observed; 13C
NMR (DMSO-d6) δ 14.0, 22.1, 25.2, 28.4, 28.6, 28.7, 28.9 (2), 29.0,
31.3, 75.1, 123.6, 125.1, 130.1, 131.3, 137.1, 152.4, 162.7, 166.8.
Anal. Calcd for C22H31NO3S: C, 67.83; H, 8.02; N, 3.60; S, 8.23.
Found: C, 67.80; H, 8.24; N, 3.56; S, 8.60.
The resulting mixture was extracted with CH2Cl2 (3 × 100 mL),
and the combined organic extracts were washed with brine (100
mL), dried (MgSO4), and passed through a short silica plug (10
cm long, 4 cm wide). The filtrate was concentrated in vacuo; the
residue was suspended in water (200 mL), and the resulting
precipitate was filtered and air-dried. This solid was then
triturated twice with boiling methanol (250 mL, 100 mL). The
combined solutions were cooled and filtered to obtain 2-(4-
cyanophenyl)-5-tridecyl-1,3,4-thiadiazole as a yellowish solid,
which was dried under reduced pressure (1.1 mmHg, P2O5, 10
h) (4.13 g, 81%): 1H NMR δ 8.07 (d, J ) 8.6 Hz, 2H), 7.77 (d, J
) 8.6 Hz, 2H), 3.17 (t, J ) 7.6 Hz, 2H), 1.85 (quint, J ) 7.5 Hz,
2H), 1.49-1.23 (m, 20H), 0.88 (t, J ) 6.6 Hz, 3H); 13C NMR δ
171.9, 166.4, 134.5, 133.0, 128.4, 118.2, 114.4, 32.0, 30.4, 30.2,
29.7 (2), 29.5 (2), 29.3, 29.1, 22.8, 14.2. Anal. Calcd for
C22H31N3S: C, 71.50; H, 8.45; N, 11.37; S, 8.68. Found: C, 71.38;
H, 8.50; N, 11.15; S, 8.97.
(S)-1-Met h ylh ep t yl 4-[4-(5-Dod ecyloxy-1,3-t h ia zolyl-2-
yl)p h en ylca r bon yloxy]ben zoa te (4). To a suspension of
compound 8 (0.622 g, 1.60 mmol), DMAP (0.0490 g, 0.402 mmol),
and phenol 9 (0.375 g, 1.50 mmol) in anhydrous CH2Cl2 (200
mL) was added DCC (0.340 g, 1.65 mmol) in one portion. The
reaction mixture was stirred at room temperature for 30 h,
diluted with hexane (50 mL), and filtered. The filtrate was
washed with 10% aq HOAc (100 mL) and brine (100 mL), dried
(MgSO4), and concentrated in vacuo. The residue was purified
by flash column chromatography (100 g of SiO2, 12:1 petroleum
ether-ethyl acetate (500 mL), followed by 9:1 petroleum ether-
ethyl acetate) to afford the title compound 4 as a white solid
(0.650 g, 70%): 1H NMR δ 8.23 (d, J ) 8.8 Hz, 2H), 8.14 (d, J )
8.8 Hz, 2H), 7.95 (d, J ) 8.5 Hz, 2H), 7.32 (d, J ) 8.5 Hz, 2H),
7.22 (s, 1H), 5.17 (app sext, J ) 6.3 Hz, 1H), 4.13 (t, J ) 6.6 Hz,
2H), 1.84 (quint, J ) 7.0 Hz, 2H), 1.68-1.78 (m, 1H), 1.55-1.68
(m, 1H), 1.35 (d, J ) 6.3 Hz, 3H), 1.24-1.53 (m, 26H), 0.89 (t, J
) 6.7 Hz, 6H); 13C NMR δ 165.6, 164.4, 163.7, 154.5, 153.4, 139.1,
131.3, 131.0, 129.3, 128.8, 125.6, 123.7, 121.8, 75.6, 72.1, 36.0,
32.1, 31.9, 29.8, 29.7 (2), 29.5, 29.4, 29.3, 29.2, 25.9, 25.6, 22.8,
22.7, 20.2, 14.3, 14.2. Anal. Calcd for C37H51NO5S: C, 71.46; H,
8.27. Found: C, 71.47; H, 8.33. Transition temperatures: Cryst.
81.5 SC*ANTI 89.0 SC*FERRI 90.6 SC*FERRO 94.9 SA 99.6 Iso. Liq.
N-(4-Br om oben zoyl)-N′-tetr adecan oh ydr azide (11). Myris-
toyl chloride (11.5 g, 46.7 mmol) was added dropwise to a
solution of 4-bromobenzohydrazide (10.0 g, 46.5 mmol) in
anhydrous pyridine (200 mL) at 10 °C under argon. The reaction
mixture was heated at 60 °C for 3 h and then concentrated in
vacuo at 70 °C. The crude residue was suspended in boiling
water (600 mL) and heated at reflux for 0.5 h. Once all of the
solid was finely suspended, the precipitate was filtered, air-dried,
and suspended in hot petroleum ether (300 mL). The cooled
suspension was filtered, and the precipitate was dried under
reduced pressure (1.1 mmHg, P2O5, 24 h) to afford the title
compound 11 as a white solid (16.4 g, 83%): 1H NMR δ 8.92 (br
s, 1H), 8.43 (br s, 1H), 7.69 (d, J ) 8.4 Hz, 2H), 7.61 (d, J ) 8.4
Hz, 2H), 2.32 (t, J ) 7.5 Hz, 2H), 1.70 (quint, J ) 7.4 Hz, 2H),
1.49-1.23 (m, 20H), 0.88 (t, J ) 6.7 Hz, 3H); 13C NMR δ 170.8,
167.3, 132.5, 129.5, 129.3, 125.4, 32.0, 30.4, 30.2, 29.8, 29.7, 29.6,
29.5, 29.3, 29.1, 22.8, 14.2. Anal. Calcd for C21H33BrN2O2: C,
59.29; H, 7.82; N, 6.59. Found: C, 59.28; H, 7.88; N, 6.52.
2-(4-Br om op h en yl)-5-tr id ecyl-1,3,4-th ia d ia zole (12). The
title compound was prepared according to the general Lawes-
son’s reagent-mediated cyclization procedure outlined above
using 8.50 g (20.0 mmol) of compound 11 and 8.91 g (22.0 mmol)
of Lawesson’s reagent. A 13 min reaction time was employed.
The cooled reaction mixture was dissolved in CH2Cl2 (250 mL)
and evaporated onto silica gel (50 g). This was then placed on
top of a short silica plug (10 cm long, 6 cm wide) and chromato-
graphed using 3:1 petroleum ether-ethyl acetate as an eluent.
The filtrate was concentrated in vacuo, and the resulting solid
was recrystallized from methanol (450 mL) to afford the title
compound 12 as fine white needles (7.67 g, 91%): 1H NMR δ
7.81 (d, J ) 8.5 Hz, 2H), 7.59 (d, J ) 8.5 Hz, 2H), 3.13 (t, J )
7.6 Hz, 2H), 1.83 (quint, J ) 7.5 Hz, 2H), 1.50-1.23 (m, 20H),
0.88 (t, J ) 6.6 Hz, 3H); 13C NMR δ 170.8, 167.3, 132.5, 129.5,
129.3, 125.4, 32.0, 30.4, 30.2, 29.8, 29.7, 29.6, 29.5, 29.3, 29.1,
22.8, 14.2. Anal. Calcd for C21H31BrN2S: C, 59.56; H, 7.38; N,
6.62; S, 7.57. Found: C, 59.53; H, 7.47; N, 6.51; S, 7.75.
2-(4-Cyanophenyl)-5-tridecyl-1,3,4-thiadiazole (3.00 g, 8.13
mmol) was heated under reflux in a solution of sodium hydroxide
(10.0 g, 0.250 mol) in ethanol (175 mL) and water (50 mL) for 3
h. A portion of the solvent (100 mL) was then distilled off at
atmospheric pressure. The remaining solvent was evaporated
in vacuo, and the beige mixture was suspended in water (350
mL). To this suspension was added 10% aq HCl (250 mL), and
the resulting white mixture was stirred for 1 h. The precipitate
was filtered off and dissolved in boiling acetic acid (100 mL).
The resulting solution was cooled by addition of ice (100 g), and
the precipitate was filtered and dried under reduced pressure
(1.1 mmHg, P2O5, 14 h) to afford the title compound 13 as a
white solid (2.94 g, 93%): 1H NMR (DMSO-d6) δ 8.07 (app s,
4H), 3.14 (t, J ) 7.6 Hz, 2H), 1.76 (quint, J ) 7.3 Hz, 2H), 1.42-
1.19 (m, 20H), 0.84 (t, J ) 6.7 Hz, 3H), the carboxylic acid signal
was not observed; 13C NMR (DMSO-d6) δ 170.9, 166.5, 166.3,
133.3, 132.7, 130.0, 127.5, 31.0, 29.1 (2), 28.8, 28.7 (2), 28.6, 28.4,
28.3, 28.0, 21.8, 13.6. Anal. Calcd for C22H31NO3S: C, 68.00; H,
8.30; N, 7.21; S, 8.25. Found: C, 67.86; H, 8.43; N, 7.09; S, 8.34.
(S)-1-Meth ylh ep tyl 4-[4-(5-Tr id ecyl-1,3,4-th ia d ia zolyl-2-
yl)p h en ylca r bon yloxy]ben zoa te (10). To a suspension of
compound 13 (0.776 g, 2.00 mmol), DMAP (0.0976 g, 0.800
mmol), and phenol 9 (0.391 g, 1.56 mmol) in anhydrous CH2Cl2
(150 mL) was added DCC (0.433 g, 2.10 mmol) in one portion.
The reaction mixture was stirred at room temperature for 1 h
and heated at reflux for 7 h. The reaction mixture was diluted
with petroleum ether (100 mL) and cooled (0 °C). The precipitate
was filtered off and washed with petroleum ether (50 mL) and
CH2Cl2 (50 mL). The combined washings and the filtrate were
evaporated in vacuo. The residue was recrystallized from 5:1
methanol-ethyl acetate (300 mL) to afford the title compound
10 as a white solid (0.530 g, 55%): 1H NMR δ 8.30 (d, J ) 8.5
Hz, 2H), 8.14 (d, J ) 8.8 Hz, 2H), 8.10 (d, J ) 8.5 Hz, 2H), 7.32
(d, J ) 8.8 Hz, 2H), 5.17 (app sext, J ) 6.2 Hz, 1H), 3.17 (t, J )
7.6 Hz, 2H), 1.86 (quint, J ) 7.4 Hz, 2H), 1.80-1.68 (m, 1H),
1.68-1.54 (m, 1H), 1.35 (d, J ) 6.1 Hz, 3H), 1.52-1.23 (m, 28H),
0.88 (t, J ) 6.6 Hz, 6H); 13C NMR δ 171.6, 167.1, 165.5, 164.0,
154.4, 135.3, 131.3, 131.1, 129.0, 128.1, 121.7, 72.1, 36.2, 32.0,
31.9, 30.4, 30.2, 29.7 (2), 29.6, 29.5, 29.3 (2), 29.1, 25.5, 22.8,
22.7, 20.2, 14.2, 14.1. Anal. Calcd for C37H51NO5S: C, 71.57; H,
8.44; N, 4.51; S, 5.16. Found: C, 71.65; H, 8.46; N, 4.51; S, 5.22.
Transition temperatures: Cryst. 93.5 SC*ANTI 101.2 SC*FERRI
102.0 SC*FERRO 104.9 SA 115.7 Iso. Liq.
Ack n ow led gm en t. We thank Dr. Mahinda Gangoda
for his help with obtaining NMR spectra and elemental
analyses.
Su p p or tin g In for m a tion Ava ila ble: General experimen-
tal procedures, procedures (or literature references) for the
synthesis of 1,4-dicarbonyl compounds employed in Lawesson’s
reagent-mediated cyclization studies, and details of purifica-
tion procedures and characterization data for all S-heterocycles
produced during these cyclization reactions. This material is
2-(4-Ca r boxyp h en yl)-5-tr id ecyl-1,3,4-th ia d ia zole (13). A
stirred solution of compound 12 (6.35 g, 15.00 mmol) and CuCN
(1.75 g, 19.5 mmol) in anhydrous NMP (36 mL) was heated at
160 °C for 21 h. The cooled reaction mixture was poured into
cooled (0 °C) 10% aq HCl (20 mL) and stirred for a short time.
J O016063X