March 2005
Nitropyridyl Isocyanates
263
(CH ), 62.8 (CH ), 113.3 (C-5), 131.8 (C-3), 142.0 (C-4), 148.0
(C-2), 152.3 (C=O), 155.1 (C-6); ms: m/z 211 (M , 39 %), 165
H-3'), 8.47 (dd, J 9.8, 2.4, 1H, H-8); 8.89 (dd, J 8.7 2.7, 1 H, H-
4'), 9.18 (d, J 2.4, 1 H, H-6), 9.46 (d, J 2.7, 1 H, H-6'); C nmr
3
2
+
13
(31), 139 (58), 137 (45), 135 (18), 121 (16), 119 (16), 93 (76), 84
(75 MHz, DMSO-d ): δ 124.1 (C-9), 124.7 (C-3´), 129.6 (C-8),
6
(97), 49 (100); HRMS (EI) calcd for C H N O , 211.05930;
observed 211.05900.
135.1 (C-6), 135.2 (C-4´), 136.5 (C-7), 144.7 (C-6´), 145.2
(C-5´), 147.1 (C-10), 151.7 (C-2´), 152.4 (C=O), 154.5 (C=O);
ms: m/z 221 (2 %), 166 (2), 165 (29), 139 (26), 135 (5), 119 (11).
109 (8), 107 (9).
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9 3 4
5-Nitropyridine-2-carbonyl azide (17).
A solution of 16 (0.3 g, 1.78 mmol) in DMF (2.5 ml) was
Anal. Calcd. for C H N O : C, 43.65; H, 1.83; N, 25.45.
12
6 6 6
added Et N (0.25 ml, 1.8 mmol) followed by the addition of
Found: C, 43.67; H, 1.98; N, 24.27.
3
diphenylphosphoryl azide (DPPA, 0.4 ml, 1.9 mmol) in DMF
(0.5 ml) over 10 min. by stirring and cooling. The solution
was stirred for 2 hrs. at 35 °C, poured over ice/CH Cl and
2-Amino-5-nitropyridine (22).
This compound was prepared from pyridine via 3-nitropyri-
dine (21) by nitration [5,6] of pyridine followed by amination [8]
according to the literature.
2
2
extracted with CH Cl . The combined organic extracts were
2
2
washed with a solution of NaHCO followed by water and
3
dried. White solid (0.3 g, 87 %) was obtained after careful
evaporation of the solvent. ir (KBr) 3097w, 3070w, 2327m,
2200m, 2141s, 1703s, 1599s, 1528s, 1355s, 1295s, 1247s,
Attempt to prepare 5-Nitro-2-pyridyl isocyanate (18) from 2-
amino-5-nitropyridine (22).
Phosgene Reaction.
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1
1184s, 1131m, 1014s, 850s, 724s, 670s cm ; H nmr (400
MHz, DMSO-d ): δ 8.32 (d, J 8.6, 1H, H-3), 8.79 (dd, J 8.6,
2-Amino-5-nitropyridine (22, 0.10 g, 0.72 mmol) in dry ethyl
6
13
2.6, 1H, H-4), 9.47 (d, J 2.6, 1H, H-6);
C nmr (75 MHz,
acetate (7 ml) was slowly added phosgene in toluene (20 % 1.5
ml, 3.3 mmol) at room temperature and refluxed for 4 hrs. The
precipitate (108 mg) was collected by filtration, dissolved in HCl
DMSO-d ): δ 125.3, 133.5, 144.9, 146.4, 151.2, 170.3; ms:
6
+
m/z 193 (M , 2 %), 165 (43), 152 (7), 151 (100), 135 (5), 124
(6), 123 (31), 119 (14), 107 (11), 92 (9), 91 (13).
(1%, 20 ml) and extracted with CH Cl yielding the dimer (20) as
2 2
off white crystals (65 mg, 20 %). The mother liquor was evapo-
rated and dissolved in ethyl acetate. Minor amounts, believed to
be the urea product (25), pure by H nmr, was obtained as yellow
5-Nitro-2-pyridyl isocyanate (18).
1
This compound was prepared from 5-nitropyridine-2-carbonyl
azide (17) as described above for the preparation of isocyanate
(9) from azide (8); ir (film) 3234w, 2388w, 2280s, 1618w, 1453w,
crystals after flash chromatography.
N,N´-di(5-nitro-2-pyridyl) urea (25).
-1
1
1330m, 1162w, 812s cm ; H nmr (400 MHz, d -benzene): δ
6
Compound 25 obtained as described above has the following
properties: ir (KBr) 3080w, 2960w, 2930w, 1735m, 1710s,
1605m, 1580m, 1520m, 1495m, 1395m, 1345s, 1300s, 1120m,
5.78 (d, J 8.9, 1H, H-3), 7.34 (dd, J 8.9, 2.8, 1H, H-4), 8.63 (d, J
2.8, 1H, H-6); ms: m/z 165 (M , 26 %), 139 (60), 123 (100), 119
+
(11), 109 (11), 100 (13), 94 (43). HRMS: calcd for C H N O ,
6
3 3 3
-1
1
855m, 770m cm ; H nmr (300 MHz, DMSO-d ): δ 8.08 (d, J
165.01744; observed 165.01746.
6
9.3, 2H, H-3), 8.64 (dd, J 9.3 2.7, 2H, H-4), 9.18 (d, J 2.7, 2H,
Ethyl 5-nitropyridyl-2-carbamate (19).
13
H-6), 10.74 (br, 2H, NH); C nmr (75 MHz, DMSO-d ): δ 111.8,
6
+
This compound was prepared from 5-nitro-2-pyridyl iso-
134.5, 139.6, 144.8, 150.8, 156.0; ms: m/z 304 (M , 1 %), 166
cyanate (18) as described above for the preparation of ethyl car-
bamate 13. Crystalline white product, pure by H nmr, (87 %
(14), 165 (83), 139 (100), 135 (9), 119 (29), 109 (15), 107 (14).
1
Oxalyl Chloride Reaction [7].
from azide 17) was obtained after recrystallization of the crude
product; mp 212-213 °C (acetone/pentane), ir (KBr) 3197m,
3140w, 2995br, 1730s, 1594s, 1561w, 1515s, 1401m, 1348s,
Oxalyl chloride (0.40 ml, 4.6 mmol) in dry ethyl acetate (2
mmol) was heated to 60 °C and added 2-amino-5-nitropyridine
(22, 0.1 g, 0.72 mmol) in dry ethyl acetate (7 ml). The precipitate
was collected by filtration after 30 min. affording the piper-
-1
1278s, 1227s, 1115m, 1062m, 1010m, 863m, 824w, 769s cm ;
1
H nmr (300 MHz, d -DMSO): δ 1.26 (t, J 7.1, 3H, CH ), 4.20
6
3
1
13
azinetetrone (23, 120 mg, 85 %), pure by H and C nmr. Trace
amounts of a by-product, believed to be the ethanediamide (24),
was observed. When the reaction was carried out at room temper-
ature, higher yields of 24 were isolated.
(q, J 7.1, 2H, CH ), 8.06 (d, J 9.4, 1H, H-3), 8.58 (dd, J 9.4, 2.8,
2
13
1H, H-4), 9.12 (d, J 2.8, 1H, H-6), 11.02 (s, br, 1H, NH); );
C
nmr (75 MHz, DMSO-d ): δ 14.3, 61.2, 111.3, 134.1, 139.4,
6
+
+
144.8, 153.3, 156.7; ms: m/z 212 (M +1, 8 %), 211 (M , 68), 166
(15), 165 (23), 152 (28), 140 (6), 139 (100), 120 (10), 119 (9),
N,N'-Di(5-nitro-2-pyridyl)piperazinetetrone (23).
109 (10); HRMS: calcd for C H N O , 211.0593; observed
8
9 3 4
Compound 23 obtained as described above has mp 280 °C
(decomp. EtOAc); ir (KBr) 3670-3250 br, 3480w, 3100m,
3070m, 2880w, 1725s, 1610m, 1570m, 1535s, 1465m, 1395m,
211.0594.
7-Nitro-3-(5-nitro-2-pyridyl)-2H-pyrido[1,2-a]-1,3,5-triazin-
2,4(3H)-dione; isocyanate dimer (20).
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1
1360s, 1310s, 1180w, 1120w cm ; H nmr (300 MHz, d -
6
DMSO): δ 7.79 (d, J 8.7, 2H, H-3), 8.91 (dd, J 8.7, 2.8, 2H, H-4),
Acyl azide 17 (76.9 mg, 0.388 mmol) in benzene (10 ml) was
13
9.52 (d, J 2.8, 2H, H-6); C nmr (75 MHz, DMSO-d ): δ 124.4,
refluxed under N atmosphere for 3 hrs. The solvent was evapo-
6
2
+
135.5, 145.0, 145.5, 150.7, 153.5; ms: m/z 386 (M , 1 %), 359
rated and the yellow crude product was recrystallised giving off
1
(2), 358 (18), 261 (1), 193 (1), 167 (1), 166 (12), 165 (100), 149
(3), 139 (4), 135 (1), 119 (40), 107 (26). HRMS: calcd for
white crystals (77 %), pure by H nmr; mp 235-237 °C (ace-
tone/pentane), ir (KBr) 3095w, 3050w, 1782m, 1698s, 1652s,
1608m, 1566s, 1529s, 1430m, 1347s, 1301w, 1273m, 1207w,
C
H N O , 386.0247; observed 386.0248.
14
6 6 8
-1
1
1132m, 1020w, 927w, 857m, 838m, 777s cm ; H nmr (300
MHz, DMSO-d ): δ 7.33 (d, J 9.8, 1H, H-9), 7.86 (d, J 8.7, 1H,
Anal. Calcd. for C H N O : C, 43.55; H, 1.57; N, 21.76.
14 6 6 8
Found: C, 43.60; H, 1.55; N, 21.86.
6