Synthesis of 5-amino-4-cyanoformimidoylimidazoles and 5-amino-4- cyanoimidazoles from amidines

Article abstract of DOI:10.1080/10426500500326982

Imidazole and formimidoylimidazole derivatives have been synthesized in high yields by a reaction between amidine and a strong or weak base depending on reaction conditions and mainly on the nature of the base used to induced cyclization. All compounds ha

Full text of DOI:10.1080/10426500500326982

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Phosphorus, Sulfur, and Silicon
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Synthesis of 5-Amino-4-
cyanoformimidoylimidazoles
and 5-Amino-4-
cyanoimidazoles from Amidines
Asieh Yahyazadeh a & Zahra Sharifi a
a Department of Chemistry, University of Guilan,
Rasht, Iran
Published online: 01 Feb 2007.
To cite this article: Asieh Yahyazadeh & Zahra Sharifi (2006) Synthesis of 5-Amino-4-
cyanoformimidoylimidazoles and 5-Amino-4-cyanoimidazoles from Amidines,
Phosphorus, Sulfur, and Silicon and the Related Elements, 181:6, 1339-1343, DOI:
10.1080/10426500500326982
To link to this article: http://dx.doi.org/10.1080/10426500500326982
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Phosphorus, Sulfur, and Silicon, 181:1339–1343, 2006
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500500326982
Synthesis of 5-Amino-4-cyanoformimidoylimidazoles
and 5-Amino-4-cyanoimidazoles from Amidines
Asieh Yahyazadeh
Zahra Sharifi
Department of Chemistry, University of Guilan, Rasht, Iran
Imidazole and formimidoylimidazole derivatives have been synthesized in high
yields by a reaction between amidine and a strong or weak base depending on
reaction conditions and mainly on the nature of the base used to induced cyclization.
All compounds have been characterized by spectroscopic data.
Keywords Amidine; anilinium hydrochloride; cyanoimidazole; diaminomaleonitrile;
formimidoylimidazole; imidate
INTRODUCTION
5-amino-4-cyanoimidazoles have long been recognized as useful syn-
thetic precursors for compounds such as a series of biologically active
purines and their derivatives,1−5 but there is no simple, general syn-
thesis available for 1-aryl derivatives of these compounds.
In 1976, Sen and Ray6 reported the synthesis of 5-amino-
4-cyano-1-(3-diethylaminopropyl)imidazole and 5-amino-4-cyano-1-
benzylimidazole via a multistep synthesis.
RESULT AND DISCUSSION
The compound 4 can be synthesised directly from the corresponding
amidine 2 under strongly basic conditions or formimidoyl-imidazole
under a weakly basic condition and then a strong base.7−11 We thus
attempted to cyclize amidines 2a–c to obtain compounds of type 3a–c
and 4a–c, which would be important intermediates for the synthesis of
a range of 9-arylpurines and 9-aryl-1,2-dihydropurines.12−14
Received May 10, 2005; accepted July 7, 2005.
Address correspondence to Asieh Yahyazadeh, University of Guilan, Department of
Chemistry, PO Box 1914, Rasht, Iran. E-mail: yahyazadeh@guilan.ac.ir
1339

1340
A. Yahyazadeh and Z. Sharifi
Imidate 1 was prepared in a high yield from diaminomaleoni-
trile and triethyl orthoformate, according to a previously described
procedure.8−10 Having obtained the imidate 1 in a good yield (94%), it
was then treated with aryl or benzylamine in a 1:1 molar ratio in ethanol
in the presence of a catalytic amount of anilinium hydrochloride9,10 to
give 2a–c. The preparation of 5-amino-1-aryl-4-cyanoimidazoles 4a–c
were attempted from the corresponding amidines 2a–c in the presence
of an aqueous potassium hydroxide solution (1M) at r.t. or DBU and an
aqueous potassium hydroxide solution (1M). The cyanoimidazoles 4a–c
were isolated in good yields (Scheme 1).
SCHEME 1 Reagents and conditions; i, RNH2, ArNH3+Cl −; ii, DBU, r.t.;
iii, KOH (1M), r.t.
Compounds 4a–c were recrystallized from
a
mixture of
ethanol/methanol (1:1) and gave pale yellow to off-white crystals,
1
respectively. These were fully characterized by TLC, IR, and H NMR
spectroscopy. The infrared spectrum confirmed the presence of the NH
and C N stretching vibrations within the region of 3400–3100 and
1660–1650 cm−1, respectively. The infrared spectrum also showed a
sharp absorption band within the range of 2220–2200 cm−1 for the C N
1
stretching vibration. In the H NMR spectra of the isolated 5-amino-
1-aryl-4-cyanoimidazoles, the primary amine protons were observed
in the region of 5.60–6.60 ppm, and in several cases the assignments
were confirmed by D2O exchange. The proton of the imidazole ring
appeared as a sharp singlet in the range of 7.14–7.42 ppm.

Imidazole and Formimidoylimidazole Derivatives
1341
EXPERIMENTAL
The 1H NMR spectra were recorded on Hitachi-Perkin-Elmer R24B (60
MHz) or Bruker XL 500 (500 MHz) instruments, and IR spectra were
recorded on a Shimadzu IR-470 spectrophotometer. Melting points were
measured on an Electrothermal digital melting point apparatus and are
uncorrected.
General Procedure for the Preparation of the
5-Amino-4-cyanoformimidoylimidazole 3a–c
To
a suspension of the corresponding aryl-(Z)-N-(2-amino-1,2-
dicyanovinyl)formamidine 2a–c7−9 (1.00 g) in dry ethanol (8 mL) DBU
(9 drops) was added. The mixture was stirred under an argon atmo-
sphere at r.t. for 0.5–3 h. After this time, TLC showed that all the
amidine had been consumed. The reaction mixture was then filtered,
washed with dry diethyl ether, and dried under vacuum to give 3a–c.
5-Amino-1-(2-chlorobenzyl)-4-cyanoformimidoylimidazole 3a
Recrystallisation of the product from dry diethyl ether and air dried in
the absence of light gave yellow crystals of 3a (0.7 g, 2.7 mmol, 71%).
m.p. 114–116◦C (decomp.); δH (500 MHz, d6-DMSO) 5.45 (s, 2H, CH2),
6.60 (s, 2H, NH2), 6.70–6.84 (m, 4H, Ar H), 7.20 (s, 1H, H-imidazole)
9.8 (br. S, 1H, NH) ppm: νmax (Nujol mull) 3420m, 3360s, 3210s, 3290s,
3160 m(N H str.), 2200s (CN str.), 1650s (C N str.), 1590s (N H bend),
1550s, 1365s, 1260s, 1210s, 1060s, 960s, 920m, 830s, 770m cm−1
.
5-Amino-1-(4-methoxyphenyl)-4-cyanoformimidoylimidazole
3b
Recrystallisation of the product from diethyl ether gave pale green crys-
tals of 3b (0.62 g, 2.57 mmol, 62%). m.p. 165–168◦C (decomp.); δH (500
MHz, d6-DMSO) 3.80 (s, 3H, OCH3), 6.10 (br. s, 2H, NH2), 6.95–7.09
(m, 4H, Ar H), 7.14 (s, 1H, H-imidazole), 9.80 (br. s, 1H, NH) ppm: νmax
(Nujol mull) 3320s, 3210s, 3190m, (N H str.), 2220s, 2210s (CN str.),
1640s (C N str.), 1570s (N H bend), 1510s, 1450s, 1280s, 860s, 815m,
820m cm−1
.
5-Amino-1-(3,4-dimethylphyneyl)-4-
cyanoformimidoylimidazole 3c
Recrystallisation of the product from diethyl ether gave pale yellow
crystals of 3c (0.82 g, 3.29 mmol, 8). m.p. 174–176◦C (decomp.); δH

1342
A. Yahyazadeh and Z. Sharifi
(500 MHz, d6-DMSO) 2.30 (s, 6H, 2 × CH3), 6.07 (br. s, 2H, NH2), 7.14
(d, 1H, H Ar), 7.21 (d, 1H, H Ar), 7.30 (d, 1H, H Ar), 7.33 (s, 1H, H-
imidazole), 8.45 (br. s, 1H, NH); νmax (Nujol mull) 3320s, 3190s (N H
str.), 3040m, 2920m, 2200s (CN str.), 1640s (C N str.), 1610s (N H
bend), 1440w, 870s, 820m cm−1
.
General Procedure for the Preparation of
5-Amino-4-cyanoimidazoles 4a–c
A suspension of the corresponding 5-amino-4-cyanoformimidoylimida-
zole 3a–c7−9 (1.00 g) in potassium hydroxide solution (1M, 10 cm3) was
stirred at r.t. until TLC showed complete consumption of the starting
material. The precipitated product was filtered, washed with water (8–
10 cm3), followed by a mixture of dry diethyl ether/ethanol (10:1), and
air-dried in the absence of light to give the desired products 4a–c.
5-Amino-1-(2-chlorobenzyl)-4-cyanoimidazole 4a
Recrystallisation of the product from dry diethyl ether/ethanol (1:1)
and air dried in the absence of light gave white crystals of 4a (0.71 g,
3.01 mmol, 80%). m.p. 112–114◦C (decomp.); δH (500 MHz, d6-DMSO)
5.40 (s, 2H, CH2), 6.60 (s, 2H, NH2), 7.01 (dd, 1H, Ar H), 7.42 (s, 1H,
H-imidazole), 7.63–7.68 (m, 2H, Ar H), 7.85 (dd, 1H, Ar H) ppm: νmax
(Nujol mull) 3400m, 3370s, 3310s, 3210s, (N H str.), 2220s (CN str.),
1650s (C N str.), 1570s (N H bend), 1520s, 1475s, 1430s, 1365s, 1280s,
1200s, 1060s, 1065s, 980s, 860m, 820m, 780s, 730m, 700m cm−1
.
5-Amino-1-(4-methoxyphenyl)-4-cyanoimidazole 4b
Recrystallisation of the product from ethanol/methanol (1:1) gave
pale yellow crystals of 4b (0.54 g, 2.5 mmol, 61%). m.p. 171–172.5◦C
(decomp.); δH (500 MHz, d6-DMSO) 3.40(s, 3H, OCH3), 5.71 (s, 2H, NH2),
6.32 (dd, 2H, (Ar H), 6.80 (dd, 2H, (Ar H), 7.14 (s, 1H, H-imidazole)
ppm: νmax (Nujol mull) 3390s, 3210s, 3160s, 3100w (N H str.), 2220s,
2210s (CN str.), 1650s (C N str.), 1610s (N H bend), 1570s, 1520s,
1260s, 1160s, 1145s, 1020s, 865s, 815m, 770s, 735m cm−1
.
5-Amino-1-(3,4-dimethylphyneyl)-4-cyanoimidazole 4c
Recrystallisation of the product from ethanol/methanol (1:1) gave pale
yellow crystals of 3c (0.72 g, 3.39 mmol, 84%). m.p. 214–215◦C (de-
comp.); δH (500 MHz, d6-DMSO) 2.27 (s, 6H, 2 × 4 CH3), 6.07 (s, 2H,
NH2), 7.2–7.14 (m, 3H, Ar H), 7.20 (s, 1H, H-imidazole); νmax (Nujol
mull) 3385s, 3350s, 3280s, 3100s (N H str.), 2220s, 2200s (CN str.),

Imidazole and Formimidoylimidazole Derivatives
1343
1660s (C N str.), 1610s (N H bend) and 1515w, 1255s, 1170s, 1155s,
1010s, 860s, 810m, 760s cm−1
.
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