Rearrangements of Alkynylamino Heterocycles
J . Org. Chem., Vol. 61, No. 10, 1996 3297
1
mp 125-126 °C; H NMR (CD3CN) 1.8 (t, 3 H), 4.2 (q, 2 H),
chloride several times, each time followed by filtration. The
filtrates were combined and concentrated under vacuum. A
brownish yellow solid weighing 4.1 g was obtained. This solid
was sublimed at 100-125 °C under 0.07 mmHg of pressure,
yield 2.9 g (48%). Further purification could be done by
slurrrying the solid with a small amount of cold, dry ether.
TLC (silica gel, dichloromethane/acetonitrile 5:1) of the solid
showed a one-spot homogeneous chromatogram: 1H NMR
(CD3CN) 4.35 (2d, 2 H), 4.95 (2t, 1 H), 6.65 (2t, 1 H), 6.8-7.2
(m, 4 H); 13C NMR (CDCl3) 144.3, 109.6, 123.4, 120.8, 105.7,
129.6 (benzene ring carbons), 121.7 (-NCHdC), 104.5
(CdCHCH2), 46.7 (CdCCH2), 153 (-NCdN-); MS m/ z at 172
(MW of 26). Anal. Calcd for C10H8N2O: C, 69.76; H, 4.68; N,
16.27. Found: C, 69.56; H, 4.89; N, 16.17.
7.15 (t, 1 H), 7.3 (t, 1 H), 7.5 (d, 1 H), 7.7 (d, 1 H). Anal. Calcd
for C11H10N2S: C, 65.32; H, 4.98; N, 13.85. Found: C, 65.10;
H, 4.99; N, 13.59.
2-(P r op a r gyla m in o)ben zoselen a zole (16). 2-Mercapto-
benzoselenazole (20.0 g, 0.093 mol) was added in portions to
sulfur monochloride (30.0 g, 0.22 mol) with stirring. After
frothing ceased, the mixture was heated to reflux for 1 h. The
dark mixture was distilled under vacuum: yield 14.0 g (70%),
reddish oil; bp 98-104 °C/0.5 mmHg. 1H NMR data ((CD3-
CN) 7.15-8.0 (m, 4 H)) were consistent with 2-chlorobenzo-
selenazole (21). 21 (2.96 g, 0.014 mol) was added to propar-
gylamine (2.0 g, 0.036 mol) while the reaction flask was chilled
in an ice bath. The mixture was warmed to rt and stirred
over a weekend. Acetone was added to the solidified mixture,
which was filtered, and the filtrate concentrated. The brown
residue was recrystallized twice from ligroin (bp 90-110 °C):
2H-4-Meth ylpyr im ido[2,1-b]ben zoxazole (27). The prepa-
ration of 27 followed a similar procedure as for compound 26
using 9 (5.58 g, 0.03 mol) and silver tetrafluoroborate (4.0 g,
0.02 mol). The reaction mixture was stirred for 7 days at rt.
The sublimed material (125-130 °C under 0.07 mmHg of
pressure) showed a homogeneous one-spot chromatogram
(silica gel, methylene chloride/acetonitrile 5:1): yield 2.5 g
1
yield 1.1 g (30%); H NMR (CD3CN) 2.55 (t, 1 H), 4.25 (d, 2
H), 6.9-7.75 (m, 4 H). Anal. Calcd for C10H8N2Se: C, 51.1;
H, 3.4; N, 11.9. Found: C, 51.3; H, 3.4; N, 12.1.
2-(N-Meth yl-N-p r op a r gyla m in o)ben zoxa zole (22). The
procedure described for preparation of compound 1 was
followed using 2-chlorobenzoxazole (3.07 g, 0.02 mol), N-
methylpropargylamine (1.38 g, 0.02 mol), triethylamine (3.03
g, 0.03 mol), and dry acetonitrile (45 mL). The crude product
was recrystallized from heptane (40 mL): yield 2.30 g (62%),
cream-colored powder; mp 67-70 °C; TLC (silica gel; dichlo-
romethane/MeOH, 98:2) single spot at Rf 0.65; 1H NMR
(CDCl3) 2.55 (t, 1 H), 3.2 (s, 3 H), 4.35 (d, 2 H), 6.8 -7.4 (m, 4
H). Anal. Calcd for C11H10N2O: C, 71.0; H, 5.4; N, 15.0.
Found: C, 70.5; H, 5.6; N, 15.0.
2-(Allyla m in o)ben zoxa zole (23). The same procedure for
compound 1 was employed using 2-chlorobenzoxazole (3.07 g,
0.02 mol), allylamine (1.14 g, 0.02 mol), triethylamine (3.03 g,
0.03 mol), and dry acetonitrile (45 mL). This gave an orange
oil whose TLC (silica gel; dichloromethane/MeOH, 98:2) showed
a major spot at Rf 0.40 and minor spots at Rf 0.90 and 0.50.
The crude product was chromatographed on silica gel using
dichloromethane/MeOH (98:2) as the eluant. Fractions con-
taining the major component were combined, and the solvent
was removed. This gave a clear oil which solidified on
1
(47%); H NMR (CD3CN) 2.26 (3d, 3 H), 4.33 (2q, 2 H), 4.76
(3q, 1 H), 7-7.3 (m, 4 H).
2H -7-Met h ylp yr im id o[2,1-b]b en zoxa zole: 1H NMR
(CD3CN) 2.3 (s, 3 H), 4.4 (m, 2 H), 5.0 (d of t, 1 H), 6.6 (d of t,
1 H), 6.85 (m, 3 H).
2H -7-Ch lor op yr im id o[2,1-b]b en zoxa zole: 1H NMR
(CD3CN) 4.4 (m, 2 H), 5.2 (d of t, 1 H), 6.65 (d of t, 1 H), 6.9-
7.2 (m, 3 H).
2H-7,8-Dich lor op yr im id o[2,1-b]ben zoxa zole: 1H NMR
(CD3CN) 4.4 (m, 2 H), 5.2 (d of t, 1 H), 6.7 (d of t, 1 H), 7.25 (s,
1 H), 7.35 (s, 1 H).
2H -7-Cya n op yr im id o[2,1-b]b en zoxa zole: 1H NMR
(CD3CN) 4.4 (m, 2 H), 5.2 (d of t, 1 H), 6.7 (d of t, 1 H), 7.25 (d,
1 H), 7.4 (d, 1 H), 7.45 (d of d, 1 H).
2H-7-(Meth oxyca r bon yl)p yr im id o[2,1-b]ben zoxa zole:
1H NMR (CD3CN) 3.85 (s, 3 H), 4.4 (m, 2 H), 5.2 (d of t, 1 H),
6.8 (d of t, 1 H), 7.2 (d, 1 H), 7.7 (d, 1 H), 7.75 (d of d, 1 H).
2H-7-(Meth ylsu lfon yl)p yr im id o[2,1-b]ben zoxa zole: 1H
NMR (CD3CN) 3.1 (s, 3 H), 4.45 (m, 2 H), 5.2 (d of t, 1 H), 6.8
(d of t, 1 H), 7.3 (d, 1 H), 7.65 (2 overlapping d, 2 H).
2H-7-Met h oxyp yr im id o[2,1-b]b en zoxa zole: 1H NMR
(CD3CN) 3.8 (s, 3 H), 4.45 (m, 2 H), 5.2 (d of t, 1 H), 6.65 (d of
d, 1 H), 6.75 (d of t, 1 H), 6.8 (d, 1 H), 7.1 (d, 1 H).
2H-4,7-Dim eth ylp yr im id o[2,1-b]ben zoxa zole: 1H NMR
(CD3CN) 2.25 (m, 3 H), 2.35 (s, 3 H), 4.3 (m, 2 H), 4.75 (m, 1
H), 6.85 (d, 1 H), 7.0 (d, 1 H), 7.15 (s, 1 H).
standing. The solid was dried in
a vacuum oven at rt
1
overnight: yield 1.66 g (48%), white solid; mp 58-61 °C; H
NMR (CDCl3) 4.1 (d of d, 2 H), 5.1-5.3 (m, 2 H), 5.9 (m, 1 H),
6.4 (bs, NH), 6.8-7.4 (m, 4 H). Anal. Calcd for C10H10N2O:
C, 68.9; H, 5.8; N, 16.1. Found: C, 68.8; H, 5.8; N, 16.0.
2-(P r op yla m in o)ben zoxa zole (24). A mixture of 23 (1.0
g, 0.0058 mol), platinum oxide (81%, 0.05 g), and ethyl acetate
(80 mL) was hydrogenated on a Parr shaker apparatus at rt.
When hydrogen uptake ceased, the mixture was filtered and
the solvent removed. The residue was recrystallized from
heptane (25 mL): yield 0.51 g (50%), white powder; mp 98-
100 °C; TLC (silica gel; dichloromethane/MeOH, 98:2) single
2H-7-Cya n o-4-m eth ylp yr im id o[2,1-b]ben zoxa zole: 1H
NMR (CD3CN) 2.2 (s, 3 H), 4.3 (t, 2 H), 4.8 (s, 1 H), 7.2 (d, 1
H), 7.4 (d, 1 H), 7.5 (s, 1 H).
2H -7-P h en ylp yr im id o[2,1-b]b en zoxa zole: 1H NMR
(CD3CN) 4.5 (m, 2 H), 5.0 (m, 1 H), 5.65 (d, 1 H), 6.8 (t, 1 H),
6.95 (t, 1 H), 7.15 (d, 1 H), 7.50 (m, 5 H).
1
spot at Rf 0.60; H NMR (CDCl3) 1.05 (t, 3 H), 1.75 (m, 2 H),
2H-2,2-Dim eth ylp yr im id o[2,1-b]ben zoxa zole (32): 1H
NMR (CD3CN) 1.4 (s, 6 H), 5.15 (d, 1 H), 6.75 (d, 1 H), 7.15
(m, 4 H).
3.45 (q, 2 H), 5.1 (bs, NH), 7.05 (t, 1 H), 7.2 (t, 1 H), 7.25 (d, 1
H), 7,4 (d, 1 H). Anal. Calcd for C10H12N2O: C, 68.2; H, 6.9;
N, 15.9. Found: C, 68.5; H, 7.0; N, 15.9.
2-(P r op a r gyla m in o)-3-m et h ylb en zoxa zoliu m H exa -
flu or op h osp h a te (25). Compound 1 (0.861 g, 0.005 mol) was
refluxed in methyl iodide (10 mL) for 25 h. Excess methyl
iodide was evaporated and the residue triturated with ether,
yield 0.76 g (48%). To an aqueous solution of this material
was added a saturated solution of potassium hexafluorophos-
phate. The precipitate was collected and dried: 1H NMR
(CD3CN) 2.8 (t, 1 H), 3.65 (s, 3 H), 4.45 (d, 2 H), 7.3-7.75 (m,
4 H). Anal. Calcd for C11H11IN2O: C, 42.1; H, 3.5; N, 8.9.
Found: C, 41.9; H, 3.6; N, 9.1.
2H-P yr im id o[2,1-b]ben zoth ia zole: 1H NMR (CD3CN)
4.35 (m, 2 H), 5.15 (m, 1 H), 6.8 (d, 1 H), 7.1 (m, 2 H), 7.3 (t,
1 H), 7.4 (d, 1 H).
2H-4-Met h ylp yr im id o[2,1-b]b en zot h ia zole: 1H NMR
(CD3CN) 2.25 (s, 3 H), 4.15 (m, 2 H), 4.85 (m, 1 H), 7.15 (t, 1
H), 7.25 (t, 1 H), 7.35 (d, 1 H), 7.45 (d, 1 H).
2H-P yr im id o[2,1-b]ben zoselen a zole: 1H NMR (CD3CN)
4.35 (m, 2 H), 5.35 (d of t, 1 H), 6.85 (d of t, 1 H), 7.1-7.7 (m,
4 H). Other peaks in the spectrum were not identified.
2H-P yr im id o[2,1-b]ben zoxa zole (26). A mixture of 1
(5.16 g, 0.03 mol) and silver tetrafluoroborate (4.0 g, 0.02 mol)
was stirred in dry acetonitrile (150 mL) at rt overnight under
nitrogen. The mixture was protected from light by aluminum
foil wrapped around the reaction flask. After 16 h, sodium
iodide (4.0 g, 0.027 mol) was added to the mixture and the
resulting mixture stirred for another 15 min and filtered. The
filtrate was concentrated under vacuum leaving behind a dull
yellow solid. This material was triturated with methylene
Ack n ow led gm en t. The authors thank Eastman
Kodak Company Analytical Technology Division for
combustion analyses. The authors are grateful to C. Y.
Chen for the preparation of compounds 10, 11, 12, and
15. The authors also wish to thank Michael R. Detty
and Stephen A. Godleski for reading the manuscript.
J O952101Z