Routes to N-vinyl-nitroimidazoles and N-vinyl-deazapurines

Article abstract of DOI:10.1002/jhet.5570410508

The preparations of 4- and 5-nitro-1-vinylimidazole (2 and 7) are described. Selective reduction of the nitro group using Fe/dil HCl is achieved for the 4-nitro derivative but this is not effective when ethoxymethylenemalononitrile is used to trap the amine. For 5-nitroimidazole studies the N-vinyl substituent is kept masked as a 2-chloroethyl group, which remains unchanged during catalytic reduction of the nitro function (Pd/C), and is revealed by HCl elimination at a later stage. In this way, the 1-deazapurine 13 and the tricyclic derivative 14 have been prepared.

Full text of DOI:10.1002/jhet.5570410508

Sep-Oct 2004
701
Routes to N-Vinyl-Nitroimidazoles and N-Vinyl-Deazapurines
*
Russell Clayton and Christopher A. Ramsden
Lennard-Jones Laboratories, School of Chemistry and Physics, Keele University, Keele,
Staffordshire ST5 5BG, England
Received April 5, 2004
The preparations of 4- and 5-nitro-1-vinylimidazole (2 and 7) are described. Selective reduction of the
nitro group using Fe/dil.HCl is achieved for the 4-nitro derivative but this is not effective when ethoxymeth-
ylenemalononitrile is used to trap the amine. For 5-nitroimidazole studies the N-vinyl substituent is kept
masked as a 2-chloroethyl group, which remains unchanged during catalytic reduction of the nitro function
(Pd/C), and is revealed by HCl elimination at a later stage. In this way, the 1-deazapurine 13 and the tricyclic
derivative 14 have been prepared.
J. Heterocyclic Chem., 41, 701 (2004).
In previous studies we have shown that aminoimida-
ative 6 with hot ethanolic NaOEt gave 5-nitro-1-vinylimi-
dazole 7 (mp 24 °C) in 54% yield. Products 6 and 7 were
both fully characterised and their 5-nitro constitutions
were confirmed by 13C nmr spectroscopy using the criteria
of McKillop and co-workers [11]. Thus, compound 7
showed 13C nmr shifts for the C-4 and C-5 imidazole ring
carbons at 133 ppm and 138 ppm respectively, which are
entirely consistent with the shifts expected for a 5-nitroim-
idazole, and in sharp contrast to those shown by the 4-nitro
isomer 2 (148 and 118 ppm).
zoles, prepared by catalytic reduction of nitroimidazoles,
are useful synthetic intermediates for the preparation of
purine analogues [1-9]. In order to extend the versatility of
this approach we have investigated the preparation of new
nitroimidazoles having synthetically useful functional
groups at various ring positions. In this paper we describe
the preparation of N-vinyl-nitroimidazoles and examples
of related N-vinyl heterocycles.
Preparations of 4- and 5-nitro-1-vinylimidazole (2 and 7)
have not previously been reported. Our initial approach to
these compounds was based on direct vinylation of 4(5)-
nitro-1H-imidazole 1. Reaction of compound 1 with hot
vinyl acetate in the presence of mercuric acetate and con-
centrated H2SO4 [10] gave a single product in 63% yield
that was identified as the 4-nitro-1-vinylimidazole 2 (mp
136 °C) (Scheme 1). Structure 2 was fully supported by ele-
mental analysis and spectroscopy. The 4-nitro constitution
of compound 2 was confirmed by 13C nmr spectroscopy:
the shifts of the imidazole ring carbon atoms at 148 ppm
(C-4) and 118 ppm (C-5) are entirely in accord with the
expected values based on a study of a series of 4- and 5-
nitroimidazole isomers by McKillop and co-workers [11].
Preparation of the 5-nitro isomer 7 required a longer
procedure involving N-protection. Heating the 1-ace-
toxymethyl derivative 3 [12] with bis-(2-chloroethyl)sul-
fate 4 and subsequent acidification gave 1-(2-chloroethyl)-
5-nitroimidazole 6 in 74% yield, presumably via the
imidazolium intermediate 5. Treatment of the chloro deriv-
Bis-(2-chloroethyl)sulfate 4 was prepared by addition of
sulfuryl chloride to a chilled solution of 2-chloroethanol (2
equiv.) in CH2Cl2. Work-up gave a clear oil that was pure
1
by H nmr analysis but which turned yellow on standing.

702
R. Clayton and C. A. Ramsden
Vol. 41
Due to the potential toxicity of this reagent it was used
immediately after preparation.
A problem associated with conversion of N-vinyl-
nitroimidazoles to the corresponding amines is the simul-
taneous reduction of the vinyl substituent. For example,
catalytic reduction of compound 2 in the presence of
ethoxymethylenemalonic acid diethyl ester (EMME) gave
the N-ethyl derivative 8 (70%). Three ethyl substituents
were clearly visible in the nmr spectra. Chemical reduction
is more selective and reduction of compound 2 with iron
powder and dilute HCl in ethanol in the presence of
EMME gave the N-vinylimidazole 9 (65%). The
unchanged N-vinyl substituent was observed in the 1H nmr
spectrum (JAX 9.8, JBX 15.7 and JAB 2.0 Hz). Attempts to
trap the 4-aminoimidazole using ethoxymethylenemaloni-
trile (EMMN), including the use of the milder reducing
agent FeCl3, were unsuccessful.
and the imidazole 2-proton are observed at δ 8.26 and δ
8.27. The N-vinyl group was then introduced by elimina-
tion of HCl using NaOEt to give compound 13 in 87%
yield. This product turns black at 250 °C and decomposes
without melting. We believe that this crystal stability, and
low solubility, is due to the high π stacking energy of the
planar conjugated system. Finally, the tricyclic derivative
14 was prepared by heating compound 13 in 95% formic
acid. This product, which was obtained in 57% yield after
recrystallisation from DMSO, was also a high melting (>
280 °C) low solubility crystalline solid.
In view of the difficulties associated with (i) in situ trap-
ping using EMMN and (ii) selective nitro group reduction,
it was decided that for further studies using 5-nitroimida-
zoles the N-vinyl group would be kept masked as an N-(2-
chloroethyl) function and generated at a later stage. At
atmospheric pressure and room temperature alkyl C-Cl
bonds are not usually reduced by catalytic hydrogenation.
Catalytic reduction of the 5-nitroimidazole 6 gave the
amine 10 which was not isolated but was trapped by addi-
tion of EMMN giving the adduct 11 (77%). As with other
5-aminoimidazoles that we have studied [1-9], the EMMN
gives exclusively the C-adduct in contrast to EMME
which gives N-adducts. In particular, the product 11 shows
a single imidazole proton (δ 7.79, C(2)H) and two amino
protons (δ 7.61). In hot ethanol containing aqueous
NaHCO3 cyclisation of the adduct 11 readily occurred to
give the 1-deazapurine 12 (65%) which was fully charac-
terised. In this product the newly formed pyridine proton
EXPERIMENTAL
1
13
The H and C nmr spectra were recorded on a Bruker
Advance DPX300 NMR spectrometer; ir spectra on a Perkin-
Elmer Paragon 1000 FT-IR spectrophotometer, mass spectra on
an AEI MS1Z spectrometer and microanalyses on a Perkin-
Elmer 240 elemental analyzer. Infrared spectra were measured as
thin films (liquids) or potassium bromide discs (solids) and nmr
spectra in deuteriochloroform (tetramethylsilane as internal stan-
dard) unless otherwise stated. Only significant bands for the ir
spectra are quoted. Melting points were determined on a
Reichert-Kofler block apparatus and are uncorrected.
4-Nitro-1-vinyl-1H-imidazole (2).
4-Nitroimidazole 1 (20.0 g, 177 mmol), mercuric acetate (2.8
g, 9 mmol) and concentrated sulphuric acid (0.86 g, 9 mmol)
were added to vinyl acetate (15.2 g, 177 mmol). The mixture was
stirred and heated under reflux (12 h) and then filtered while hot.
The resulting cloudy solution was evaporated to give a beige
solid that was recrystallised from ethanol and identified as the 4-

Sep-Oct 2004
Routes to N-Vinyl-Nitroimidazoles and N-Vinyl-Deazapurines
703
nitroimidazole 2 (15.4 g, 63%), small cream needles, mp 136 °C;
ir (KBr): 826, 913, 982, 1142, 1292, 1323, 1348, 1492, 1514,
(2H, t, J 5.5 Hz, ClCH ), 4.76 (2H, t, J 5.5 Hz, NCH ), 7.83 (1H,
2
d, J 0.9 Hz, imidazole C(4)H), 8.01 (1H, d, J 0.9 Hz, imidazole
2
-1
1
1543, 1648, 3120 and 3160 cm ; H nmr (DMSO-d ): δ 5.21
13
C(2)H); C nmr: δ 43.0 (ClCH ), 49.5 (NCH ), 134.0 (C(4)H),
2 2
6
(1H, dd, J 1.0 and 8.9 Hz, CH=CH (cis)), 5.91 (1H, dd, J 1.0 and
+
138.3 (C(5)), 143.1 (C(2)H); ms: m/z 175(78%)(M ), 140, 113,
98, 67, 63(100%), 53, 40, 27.
Anal. Calcd for C H Cl N O : C, 34.20; H, 3.44; N, 23.93.
2
15.8 Hz, CH=CH (trans)), 7.23 (1H, dd, J 8.9 and 15.8 Hz, N-
2
CH=CH ), 8.10 (1H, s, imidazole C(2)H), 8.30 (1H, s, imidazole
2
5
6
3 2
13
C(5)H); C nmr (DMSO-d ): δ 106.0 (C=CH ), 118.1 (C(5)H),
Found: C, 34.36; H, 3.48; N, 24.23.
6
2
129.3 (C=CH), 136.0 (C(2)H), 147.9 (C(4)); ms: m / z
5-Nitro-1-vinyl-1H-imidazole (7).
+
+
140(26%)(M+1 ), 139(100%)(M ), 54, 52, 39, 30, 27.
Anal. Calcd for C H N O : C, 43.17; H, 3.62; N, 30.21.
Found: C, 43.10; H, 3.50; N, 30.24.
Sodium ethoxide (1.02 g, 15.0 mmol) was added to 1-(2-
chloroethyl)-5-nitroimidazole 6 (1.76 g, 10.0 mmol) in refluxing
EtOH (100 ml, anhydrous). The resulting orange solution was
heated under reflux (30 minutes) before cooling to room temper-
ature and stirring overnight. The precipitate was removed and the
solution reduced in volume (10 ml) and partitioned between
5
5 3 2
1-Acetoxymethyl-4-nitro-1H-imidazole (3).
A mixture of toluene (40 ml), acetic anhydride (9 ml, 95
mmol), glacial acetic acid (1.6 ml, 28 mmol), 4(5)-nitroimidazole
(8.96 g, 79 mmol), paraformaldehyde (2.86 g, 95 mmol) and
sodium acetate (0.26 g, 3.2 mmol) was stirred at 100 °C (90 h).
The solution was evaporated and the solid residue partitioned
water (200 ml) and Et O (200 ml). The organic phase was sepa-
2
rated, dried and reduced to a yellow oil. Column chromatography
(silica gel; Et O as eluent) gave the nitroimidazole 7 (0.75 g,
2
54%), yellow crystalline solid, mp 24 °C; ir (film): 643, 826,
between water (150 ml) and CHCl (150 ml). The organic layer
3
was dried (MgSO ), evaporated and the product recrystallised
-1
1
1119, 1526, 1376, 1473, 1530, 1641 and 3127 cm ; H nmr: 5.36
(1H, dd, J 1.8 and 8.4 Hz, CH=CH (cis)), 5.57 (1H, dd, J 1.8 and
15.5 Hz, CH=CH (trans)), 7.44 (1H, dd, J 8.4 and 15.5 Hz,
4
from ethyl acetate and identified as compound 3 (12.2 g, 83%),
colourless crystals, mp 80 °C (Lit.[12] mp 83.5-84.5 °C) ; ir
(KBr): 757, 823, 982, 1143, 1222, 1491, 1543, 1753 and 3095
2
2
NCH=CH ), 7.85 (1H, d, J 0.8 Hz, imidazole(4)-H), 8.00 (1H, d,
13
2
J 0.8 Hz, imidazole(2)-H); C nmr (DMSO-d ): 110.1 (=CH ),
-1
1
cm ; H nmr: δ 2.09 (3H, s, CH ), 5.83 (2H, s, CH ), 7.61 (1H,
3
d, J 1.5 Hz, imidazole C(5)H), 7.93 (1H, d, J 1.5 Hz, imidazole
2
6
128.8 (=CH), 133.2 (C(4)H), 138.0 (C(5)), 140.2 (C(2)H); ms:
2
+
13
C(2)H); C nmr: δ 20.5 (COCH ), 68.8 (CH ), 121.9 (C(5)H),
m/z 139(48%)(M ), 94(37), 82(17), 67(30), 66(56), 55(24),
54(46), 40(44), 39(100), 28(91), 27(49).
3
138.4 (C(2)H), 147.4 (C(4)), 170.0 (C=O); ms: m / z
2
+
185(59%)(M ), 155, 127, 126, 97, 73(100%), 68.
Anal. Calcd for C H N O : C, 38.92; H, 3.81; N, 22.70.
Anal. Calcd. for C H N O : C, 43.17; H, 3.62; N, 30.21.
5 5 3 2
Found C, 43.44; H, 3.50; N, 30.19.
6
Found: C, 38.76; H, 3.67; N, 22.69.
7 3 4
2-[(1-Ethyl-1 H-imidazol-4-ylamino)-methylene]-malonic Acid
Diethyl Ether (8).
Sulfuric Acid Bis-(2-chloroethyl) Ester (4).
4-Nitro-1-vinylimidazole 2 (1.39 g, 10 mmol), ethoxymethyl-
enemalonic acid diethyl ester (EMME) (2.16 g, 10 mmol) and
5% Pd/C (0.87 g, 50% w/w) were placed in dry 1,4-dioxane (35
ml). The mixture was hydrogenated at atmospheric pressure with
vigourous shaking until the uptake of hydrogen had ceased
(approx. 680 ml). The mixture was filtered through celite to yield
a yellow solution which was concentrated and purified by col-
umn chromatography (silica gel; EtOAc:60-80 pet. ether; 1:1 as
eluent). The largest fraction was collected, recrystallised from
ethyl acetate:hexane and identified as the N-ethylimidazole 8
(1.97 g, 70%), yellow crystals, mp 63 °C; ir (KBr): 791, 996,
Sulphuryl chloride (122.8 g, 0.91 mol) was added dropwise (2
h) to a solution of 2-chloroethanol (146 g, 1.82 mol) in CH Cl
2
2
(250 ml) in an ice bath. The solution was stirred (2 h), washed
with water (250 ml) and then the solvent was removed. The
resulting crude oil was placed in a separating funnel with water
(250 ml) and petroleum ether (bp 40-60 °C) (250 ml).
Dichloromethane was then added to the triphasic mixture in 10
ml aliquots, until, with shaking, the mixture became biphasic.
The organic fraction was removed and washed with sat. NaHCO
3
solution (200 ml), water (200 ml) and then dried (Na SO ).
2
Removal of solvent under reduced pressure yielded a clear oil,
4
-1
1095, 1256, 1311, 1424, 1620, 1648, 1694, 2978 and 3119 cm ;
1
which discoloured on standing, that was identified as the ester 4
1
(138 g, 68%); H nmr: 3.84 (4H, t, J 5.6, Cl-CH ), 4.71 (4H, t, J
H nmr: δ 1.30 (3H, t, J 7.1 Hz, OCH CH ), 1.36 (3H, t, J 7.1 Hz,
2
OCH CH ), 1.45 (3H, t, J 7.3 Hz, NCH CH ), 3.94 (2H, q, J 7.3
3
2
5.6, O-CH ). This material was used without further purification.
2
Hz, NCH CH ), 4.21 (2H, q, J 7.1 Hz, OCH CH ), 4.26 (2H, q,
3
2
3
2
2
J 7.1 Hz, OCH CH ), 6.60 (1H, d, J 1.2 Hz, imidazole C(5)H),
3
2
3
1-(2-Chloroethyl)-5-nitro-1H-imidazole (6).
2
7.28 (1H, d, J 1.2 Hz, imidazole C(2)H), 8.70 (1H, d, J 13.6 Hz,
3
1-Acetoxymethyl-4-nitroimidazole 3 (18.5 g, 100 mmol) and
sulfuric acid bis-(2-chloroethyl) ester 4 (2.05 g, 112 mmol) were
heated at 100 °C (2 h). The biphasic mixture was then transferred
13
NHCH), 10.94 (1H, d, J 13.6 Hz, CHNH); C nmr: δ 14.4
(CH ), 14.5 (CH ), 16.2 (CH ), 42.4 (CH ), 59.7 (CH ), 60.2
3
3
3
2
2
(CH ), 92.0 (C), 103.7 (CH), 134.1 (CH), 140.3 (C), 152.5 (CH),
to a flask containing 10% aqueous H SO (70 ml) and heated
2
4
2
165.6 (C), 169.3 (C); ms: m/z 281(63%)(M ), 235, 190(100%),
+
under reflux (2 h). The reaction mixture was cooled and diluted
with water (100 ml). Aqueous NaOH (10%) was added cau-
tiously, with stirring in an ice bath, to pH 11. Extraction with
CH Cl (3 x 100 ml), followed by drying (Na SO ) and removal
163, 141, 135, 122, 56, 56, 29.
Anal. Calcd. for C H N O : C, 55.50; H, 6.81; N, 14.94.
13 19 3 4
Found: C, 55.59; H, 6.93; N, 14.93.
2
2
2
4
of solvent yielded a pale yellow oil which crystallised slowly at
room temperature. This product was recrystallised from H O and
2-[(1-Vinyl-1H-imidazol-4-ylamino)-methylene]-malonic Acid
Diethyl Ether (9).
2
identified as the 5-nitroimidazole 6 (13.0 g, 74%), pale yellow
rectangular crystals, mp 49 °C; ir (KBr): 656, 744, 1121, 1268,
4-Nitro-1-vinylimidazole 2 (1.39 g, 10 mmol), ethoxymethyl-
enemalonic acid diethyl ester (EMME) (2.16 g, 10 mmol), hydro-
-1
1372, 1435, 1466, 1528, 3098 and 3122 cm ; H nmr: δ 3.94
1

704
R. Clayton and C. A. Ramsden
Vol. 41
gen reduced iron powder (3.0 g), concentrated hydrochloric acid
(0.1 ml) and water (10 ml) were placed in EtOH (40 ml) and the
solution heated to reflux. The reaction was monitored by tlc until
all the vinylimidazole had been consumed. The reaction mixture
was then cooled, filtered through celite and concentrated.
Column chromatography (silica gel: EtOAc:60-80 pet. ether; 1:1
as eluent) gave a solid that was identified as the vinylimidazole 9
(1.80 g, 65%), yellow solid, mp 56 °C; ir (KBr): 598, 675, 790,
1081, 1239, 1267, 1570, 1622, 1651, 1699, 2978, 3099 and 3124
13
zole C(2)H); C nmr (DMSO-d ): δ 42.5 (CH ), 44.4 (CH ),
6
85.8 (C), 117.8 (C), 126.6 (C), 134.0 (CH), 144.3 (CH), 149.0
2
2
+
(C), 157.6 (C); ms: m/z 221(84%)(M ), 172, 159(100%), 104,
63, 28.
Anal. Calcd for C H ClN : C, 48.77; H, 3.64; N, 31.60.
9
8
Found: C, 48.89; H, 3.67; N, 31.89.
5
5-Amino-3-vinyl-3H-imidazo[4,5-b]pyridine-6-carbonitrile (13).
5-Amino-3-(2-chloroethyl)-imidazo[4,5-b]pyridine-6-carboni-
trile 12 (1.11 g, 5.0 mmol) was dissolved in hot dry EtOH (50 ml)
and sodium ethoxide (0.4 g, 5.9 mmol) was added with rapid stir-
ring. The solution was then heated under reflux and the reaction
monitored by tlc. Extra portions of sodium ethoxide (0.15 g, 1.5
mmol) were added until all the starting material was consumed.
The mixture was cooled and the precipitate collected. The solid
product was washed repeatedly with water (5 x 50 ml), dried
under vacuum and identified as the vinyl-imidazo[4,5-b]pyridine
13 (805 mg, 87%), buff crystals (EtOH), mp 251 °C (dec.); ir
(KBr): 880, 1243, 1303, 1416, 1437, 1509, 1570, 1634, 2211,
-1
1
cm ; H nmr: δ 1.23 (3H, t, J 7.1 Hz, CH -CH ), 1.29 (3H, t, J
2
3
7.1 Hz, CH -CH ), 4.14 (2H, q, J 7.1 Hz, CH -CH ), 4.21 (2H, q,
2
J 7.1 Hz, CH - C H ), 4.84 (1H, dd, J 2.0 and 9.8 Hz,
3
3
2
3
2
C H = C H (c i s )), 5.17 (1H, dd, J 2.0 and 15.7 Hz,
2
CH=CH (trans)), 6.78 (1H, dd, J 9.8 and 15.7 Hz, NCH=CH ),
2
2
6.83 (1H, d, J 1.4 Hz, imidazole C(5)H), 7.40 (1H, d, J 1.4 Hz,
imidazole C(2)H), 8.64 (1H, d, J 13.4 Hz, NHCH), 10.91 (1H, d,
13
J 13.4 Hz, CHNH); C nmr: δ 14.3 (CH ), 14.5 (CH ), 59.9
3
(CH ), 60.3 (CH ), 92.8 (C), 100.1 (CH), 101.8 (CH ), 129.0
3
2
(CH), 134.3 (CH), 141.0 (C), 152.1 (CH), 165.4 (C), 169.1 (C);
2
2
+
-1
1
ms: m/z 279(50%)(M ), 233, 188, 161(100%), 133, 120, 54 , 29,
28, 27.
Anal. Calcd for C H N O : C, 55.91; H, 6.14; N, 15.05.
3104, 3158, 3296 and 3480 cm ; H nmr (DMSO-d ): δ 5.20
6
(1H, d, J 8.9 Hz, CH=CH (cis )), 6.13 (1H, d, J 15.9 Hz,
2
CH=CH (trans)), 7.01 (2H, s, NH ), 7.29 (1H, dd, J 8.9 and 15.9
13 17
3 4
Found: C, 55.84; H, 6.38; N, 14.65.
2
Hz, NCH=CH ), 8.40 (1H, s, pyridine C(7)H), 8.64 (1H, s, imi-
2
2
dazole C(2)H); C nmr (DMSO-d ): δ 86.8 (C), 103.6 (CH ),
13
6
2
118.1 (C), 127.2 (CH), 127.5 (C), 134.8 (CH), 142.2 (CH), 148.3
2-[5-Amino-1-(2-chloroethyl)-1H-imidazol-4-ylmethylene]-mal-
ononitrile (11)
+
(C), 158.4 (C); ms: mz 185(100%)(M ), 158, 131, 78, 28.
Anal. Calcd for C H N : C, 58.37; H, 3.81; N, 37.82. Found:
A mixture of 1-(2-chloroethyl)-5-nitroimidazole 6 (1.75 g, 10
mmol) and 5% Pd/C (0.87 g, 50% w/w) in dry 1,4-dioxane (35
ml) was hydrogenated at atmospheric pressure with vigourous
shaking until uptake of hydrogen (approx. 680 ml) had ceased.
The mixture was filtered through celite to yield a yellow solution
that darkened to orange. A solution of ethoxymethylene mal-
ononitrile (1.22 g, 10 mmol) in 1,4-dioxane (20 ml) was added
and the mixture was stirred overnight under a nitrogen atmos-
phere. The resulting yellow precipitate was collected, washed
with dioxane and, after drying under vacuum, identified as the
imidazole derivative 11 (1.71 g, 77%), bright yellow solid, mp
190-192 °C; ir (KBr): 846, 1121, 1338, 1462, 1560, 1604, 1656,
9 7 5
C, 58.45; H, 3.81; N, 37.65.
3,7-Dihydro-3-vinylimidazo[4',5':5,6]pyrido[2,3-d]pyrimidin-8-
one (14).
5-Amino-3-vinylimidazo[4, 5 -b]pyridine-6-carbonitrile 13
(740 mg, 4.0 mmol) was dissolved in 95% formic acid (50 ml)
and heated under reflux (24 h). The reaction mixture was then
reduced to a volume of approximately 5 ml and diluted with
water (50 ml). The solution was adjusted to pH 7 using 2 M aque-
ous NaOH and chilled overnight. The solid precipitate was col-
lected and dried. Recrystallisation from DMSO gave a light
brown solid that was identified as the imidazo[4',5':5,6]-
pyrido[2,3-d]pyrimidin-8-one 14 (477 mg, 56%), m.p. > 280 °C;
-1
1
2204, 2220, 2927, 3336 and 3456 cm ; H nmr (DMSO-d ): δ
6
3.87 (2H, t, J 5.8 Hz, ClCH ), 4.18 (2H, t, J 5.8 Hz, NCH ),
2
2
7.54 (1H, s, C=CH), 7.61 (2H, s, NH ), 7.79 (1H, s, imidazole
-1
ir (KBr): 3453, 2628, 1688, 1602, 1401, 1264, 922 and 805 cm ;
1
2
C ( 2 )H); C nmr (DMSO-d ): δ 42.1 (CH ), 44.3 (CH ), 57.6
13
H nmr (DMSO-d ): δ 5.20 (1H, d, J 8.9 Hz, CH=CH (cis)), 6.13
6
(1H, d, J 15.9 Hz, CH=CH (trans)), 7.29 (1H, dd, J 8.9 and 15.9
2
6
(C), 116.4 (C), 118.0 (CN), 118.8 (CN), 138.1 (C(2)H), 143.2
2
2
2
Hz, NCH=CH ), 8.40 (1H, s, pyridine-H), 8.64 (1H, s, imida-
+
(C), 150.3 (C=CH); ms: m/z 221(64%)(M ), 172, 159(100%),
118, 104, 63, 28.
Anal. Calcd. for C H ClN : C, 48.77; H, 3.64; N, 31.60.
2
z o l e -H); ms: m/z 213(100%)(M ), 186(98), 160(21), 131(11),
+
104(9), 78(12), 63(13), 54(10), 52(8), 27(10); HRMS.
+
9
Found: C, 48.49; H, 3.57; N, 31.65.
8
5
C H N O: M calc. 213.0651, found 213.0650
10 7 5
5-Amino-3-(2-chloroethyl)-3H-imidazo[4,5-b]pyridine-6-car-
bonitrile (12).
Acknowledgment.
We thank Scotia Pharmaceuticals for financial support and the
EPSRC National Mass Spectrometry Service for mass spectra.
2-[5-Amino-1-(2-chloroethyl)-imidazol-4-ylmethylene]-mal-
ononitrile 11 (1.71 g, 77.3 mmol) and 5% aqueous sodium bicar-
bonate (1 ml) were placed in EtOH (30 ml) and heated under
reflux with stirring (1 h). The mixture was allowed to cool slowly
and the product was collected, washed with cold EtOH (2 x 40
ml), dried under vacuum and identified as the imidazo[4,5-
b]pyridine 12 (1.12 g, 65%), golden crystals (EtOH), mp 231 °C;
ir (KBr): 668, 763, 913, 1156, 1304, 1429, 1517, 1570, 1636,
REFERENCES AND NOTES
[1] A. H. M. Al-Shaar, D. W. Gilmour, D. J. Lythgoe, I.
McClenaghan and C. A. Ramsden, J. Chem. Soc., Perkin Trans. I, 2779
(1992).
[2] A. H. M. Al-Shaar, R. K. Chambers, D. W. Gilmour, D. J.
Lythgoe, I. McClenaghan and C. A. Ramsden, J. Chem. Soc., Perkin
Trans. I, 2789 (1992).
-1
1
2212, 2924, 3186, 3305 and 3475 cm ; H nmr (DMSO-d ): δ
6
4.07 (2H, t, J 6.0 Hz, ClCH ), 4.45 (2H, t, J 6.0 Hz, NCH ), 6.82
2
(2H, s, NH ), 8.26 (1H, s, pyridine C(7)H), 8.27 (1H, s, imida-
2
[3] D. J. Lythgoe and C. A. Ramsden, Adv. Heterocyl. Chem., 61,
2

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Routes to N-Vinyl-Nitroimidazoles and N-Vinyl-Deazapurines
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