Synthesis of aryl(or benzyl)-(Z)-N-[2-amino-1,2-dicyanovinyl]formamidines

Article abstract of DOI:10.1081/SCC-120013752

Starting from readily available ethyl(Z)-N-(2-amino-1,2-dicyanovinyl)formimidate (1), the N-aryl (or benzyl)-N′(-(2-amino-1,2-dicyanovinyl)formamidines (2) can be prepared in good yields by reaction with aromatic amines at room temperature in the presence of a catalytic amount of aniline hydrochloride.

Full text of DOI:10.1081/SCC-120013752

Synthetic Communications
An International Journal for Rapid Communication of Synthetic Organic
Chemistry
ISSN: 0039-7911 (Print) 1532-2432 (Online) Journal homepage: http://www.tandfonline.com/loi/lsyc20
SYNTHESIS OF ARYL(OR BENZYL)- (Z)-N-[2-
AMINO-1,2-DICYANOVINYL]FORMAMIDINES
Asieh Yahya-Zadeh & Brian L. Booth
To cite this article: Asieh Yahya-Zadeh & Brian L. Booth (2002) SYNTHESIS OF ARYL(OR
BENZYL)- (Z)-N-[2-AMINO-1,2-DICYANOVINYL]FORMAMIDINES, Synthetic Communications,
32:20, 3241-3246, DOI: 10.1081/SCC-120013752
To link to this article: http://dx.doi.org/10.1081/SCC-120013752
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SYNTHETIC COMMUNICATIONS
Vol. 32, No. 20, pp. 3241–3246, 2002
SYNTHESIS OF ARYL(OR BENZYL)-
(Z)-N-[2-AMINO-1,2-
DICYANOVINYL]FORMAMIDINES
Asieh Yahya-Zadeh1, and Brian L. Booth2
*
1Department of Chemistry, University of Guilan,
P.O. Box 1914, Rasht, Iran
2Department of Chemistry, University of Manchester
Institute of Science and Technology,
Manchester M60 1QD, UK
ABSTRACT
Starting from readily available ethyl(Z)-N-(2-amino-1,2-dicya-
novinyl)formimidate (1), the N-aryl (or benzyl)-N0(-(2-amino-
1,2-dicyanovinyl)formamidines (2) can be prepared in good
yields by reaction with aromatic amines at room temperature
in the presence of a catalytic amount of aniline hydrochloride.
Amidines are an important class of compounds which have proved to
be intermediates in a number of biological processes.[1–3] The chemistry and
preparation of amidines have been reviewed by Shriner and Neumann.[4]
Synthesis and characterization of several alkyl, aryl amidine and also the
amidrazone have been reported previously.[5–7] We decided that we could
*Corresponding author. E-mail: yahyazedah@cd.gu.ac.ir
3241
DOI: 10.1081/SCC-120013752
Copyright & 2002 by Marcel Dekker, Inc.
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3242
YAHYA-ZADEH AND BOOTH
Scheme 1.
prepared various aryl and benzyl amidines of type (2a–2d) by reaction of
imidate (1) with aromatic amines.
In order to synthesis the required amidines (2a–2d), the following
method, which involves treatment of imidate (1) with the appropriate aryl
or benzyl amine, was used Sch. 1. Ethyl(Z)-N-(2-amino-1,2-dicyanovinyl)-
formimidate (1) was prepared according to a previously reported procedure
by treatment of equimolar quantities of triethylorthoformate and diamino-
maleonitrile in refluxing dioxane.[6,8–9]
Having obtained the imidate (1) in 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 aniline hydrochloride. The reaction
mixture was stirred under an inert atmosphere at room temperature with
the exclusion of light. A homogeneous solution was obtained and within
10 min a white solid precipitated out. The product was filtered off after
3–4 h. It was washed with diethyl ether and was found be pure by TLC,
1H and 13C NMR spectroscopy.

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SYNTHESIS OF FORMAMIDINES
3243
The elemental analysis results of amidine (2) were satisfactory.
The mass spectrum showed a peak at m/z 260, 286, 272 and 242 for 2a,
2b, 2c and 2d, respectively. Initial fragmentation, involve loss of the amidine
1
segment (M-C5H4N5)þ. The H NMR spectra of compound 2a and 2b in
[2H6]dimethyl sulfoxide ([2H6]DMSO) had some interesting features.
The two benzylic protons (H6) appeared as a doublet at ꢀ 4.58 and ꢀ
4.68 ppm respectively, caused by a coupling to the NH proton which
appeared as a broad doublet at ꢀ 8.08–8.16 ppm. The HC¼N proton was
also a doublet (JH,NH 6.0–6.5 Hz), at ꢀ 7.62–7.78 ppm and showed a small
additional coupling (<1 Hz) to the benzylic protons. The fact that the
HC¼N and the benzylic protons are coupled to NH was also confirmed
by D2O exchange, after which the two doublets (HC¼N & CH2) appeared
as sharp singlets. The 13C NMR spectrum show two peaks of relatively low
intensity at ꢀ 118.8–120.1 and ꢀ 119.9–121.4 ppm due to the two cyano
groups and a peak due to HC¼N at ꢀ 149.0–154.5 ppm in the amidine
molecule. The infrared spectrum of amidine (2a–2d) showed two strong
absorption in the region 2195–2230 cmꢀ1 characteristic of CN stretching
vibrations, together with an NH and a C¼N stretching vibration at
3480–3120 and 1655–1640 cmꢀ1 respectively.
EXPERIMENTAL
1
The H NMR spectra were recorded on Hitachi-Perkin-Elmer R24B
(60 MHz) or Bruker XL 300 (300 MHz) instruments (with J-values given
in Hz), 13C NMR spectra (with DEPT 135) either on a Bruker WP80 or

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3244
YAHYA-ZADEH AND BOOTH
XL300 instrument, and IR spectra on a Shimadzu IR-435 spectropho-
tometer. Mass spectra were recorded on a Kratos Concept instrument.
The melting points were measured on an Electrothermal digital melting
point apparatus and are uncorrected.
General procedure for the preparation of the N-aryl-N0-[2-amino-1,2-
dicyanovinyl]formamidines (2a–2d): The aromatic amine (1.01 g, 6.07 mmol)
was added to a suspension of 1 (1.00 g, 6.09 mmol) in dry ethanol or
ethyl acetate, which contained aniline hydrochloride (0.02). The mixture
was stirred at room temperature until TLC (9 : 1 chloroform/ethanol
eluant) showed that all the formimidate had disappeared (usually 3–4 h)
and the amidine was isolated by filtration. The most cases the product was
pale green to white. The precipitate was washed with dry diethyl ether and
was dried under vacuum to give the analytically pure products (2a–2d).
(2-Chlorobenzyl)-(Z)-N-[2-amino-1,2-dicyanovinyl]formamidine (2a):
M.p. 108–110ꢁC (decomp.). Yield 92%. [Found C, 55.5; H, 3.7; N, 27.3; Cl,
13.6. Calc. for C12H10N5Cl requires C, 55.6; H, 3.8; N, 27.0; Cl, 13.5%]; m/z
(FAB) 260 (M þ 1)þ 65.5%, 259 (M)þ 78%, 224 (M-Cl)þ 18.2%, 165 [(M-1)-
C4H3N3]þ 100%, 164 (M-C4H4N3]þ 90.8%, 142 (12.12%), 125 (81.8%), 119
(30.3%), 109 (9.0%); ꢀH (300 MHz, d6-DMSO, TMS Int. Ref.) 4.58 (d, 2H,
3J6,NH 6.5 Hz, H6), 6.80 (s, 2H, NH2), 7.40–7.44 (complex m, 2H, H11 &
H12), 7.45–7.56 (complex m, 2H, H9 & H10), 7.78 (d,1H, 3J5,NH 6.5 Hz, H5),
3
8.16–8.24 (br.d, 1H, JNH,5 6.5 Hz, NH) ppm; ꢀC (75 MHz, d6-DMSO) 45.9
(C6), 110.0 (C1), 119.1 (C2), 120.1 (C3), 121.4 (C4), 131.2 (C11), 132.9 (C12),
133.0 (C10), 133.5 (C9), 136.6 (C8), 139.7 (C7), 154.5 (C5) ppm; ꢁmax (Nujol
mull) 3420 s, 3380 s, 3320 s, 3180 m (NH str.), 3000 m, 2980 m, 2950 m, 2220 s
(CN str.), 2200 s (CN str.), 1655 s (C¼N str.), 1580 m (NH bend), 1470 m,
1460 s, 1450 s, 1430 m, 1380 s, 1360 s, 1260 s, 1235 w, 1220 w, 1170 m, 1060 s,
1040 s, 1015 s, 980 w, 950 s, 815 s, 790 m, 760 s cmꢀ1
.
(3,4-Dimethoxybenzyl)-(Z)-N-[2-amino-1,2-dicyanovinyl]formamidine
(2b): M.p. 124–126ꢁC (decomp.). Yield 94%. [Found C, 59.2; H, 5.5; N,
24.3. Calc. for C14H15N5O2: C, 58.9; H, 5.3; N, 24.6%]; m/z (EI) 286
(M þ 1)þ 3.2%, 245 [(M þ 1)-CH2N2]þ 1.8%, 168 [(M þ 1)-C5H2N4]þ
9.8%, 151 (M-C5H4N5)þ 100%; ꢀH (300 MHz, d6-DMSO) 3.95 (s, 3H,
3
OCH3), 3.97 (s, 3H, OCH3), 4.68 (d, 2H, J6,NH 6 Hz, H6), 6.40 (s, 2H,
3
NH2), 6.78–7.02 (m, 3H, H8, H9 & H12), 7.62 (d, 1H, J5,NH 6 Hz, H5),
3
8.08–8.16 (br, d, 1H, J5,NH 6 Hz, NH) ppm; ꢀC (75 MHz, d6-DMSO) 43.9
(C6, by DEPT 135), 55.5 and 55.7 (C13 & C14), 110.4 (C1), 115.8 and 116.1
(C9, C12), 119.3 and 120.4 (C3 & C4), 121.1 (C2), 124.1 (C8), 135.2 (C7),
152.0 and 152.7 (C10 & C11), 154.4 (C5) ppm; ꢁmax (Nujol mull) 3480 s,
3380 s (NH str.), 2225 s (CN str.), 2205 s (CN str.), 1645 s (C¼N str.), 1600
m (NH bend), 1520 m, 1275 s, 1250 m, 1230 w, 1170 s, 1155 w, 1040 s, 980 m,
965 w, 880 s, 850 s, 815 s, 780 s cmꢀ1
.

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SYNTHESIS OF FORMAMIDINES
3245
(3,4-Dimethoxyphenyl)-(Z)-N-[2-amino-1,2-dicyanovinyl]formamidine
(2c): M.p. 138–140ꢁC (decomp.). Yield 96%. [Found C, 57.9; H,4.8; N, 25.4.
Calc. for C13H13N5O2: C, 57.6; H, 4.8; N, 25.8%]; m/z (EI) 272 (M þ 1)þ
8.9%, 271 (M)þ 47.8%, 270 (M ꢀ 1)þ 11.0%, 244 [(M ꢀ 1)-CN]þ 32.9%, 164
[(M-1)-C4H2N4]þ 37.6%; ꢀH (300 MHz, d6-DMSO) 3.60 (s, 6H, 2 ꢂ OCH3),
3
6.25 (br.s, 2H, NH2), 6.76 (d, 1H, J8,7 8.5Hz, H8), 7.45–7.70 (br. complex
m, 3H, H7, H11 & H5), 9.70 (br.s, 1H, NH) ppm; ꢀC (75MHz, d6-DMSO)
59.4 and 59.7 (C12 &C13), 110.0 (C1), 116.0 (C7), 116.3 (C8), 116.6 (C11),
119.0 and 120.0 (C3 & C4), 122.5 (C2), 137.1 (C6), 149.0 (C5), 153.0 and
153.3 (C9 & C10) ppm; ꢁmax (Nujol mull) 3470 s, 3340 s, 3235 s (NH str.),
2230 s (CN str.), 2195 s (CN str.), 1640 m (C ¼ N str.), 1600 m (NH bend),
1580 s, 1510 s, 1300 s, 1255 s, 1230 s, 1165 s, 1145 s, 1130 s, 1025 s, 965 w,
935 s, 830 s, 795 s, 765 s cm-1.
(4-Methoxyphenyl)-(Z)-N-[2-amino-1,2-dicyanovinyl]formamidine (2d):
M.p. 123–124ꢁC (decomp.). Yield 93%. [Found C, 59.7; H, 4.5; N, 28.7.
Calc. for C12H11N5O C, 59.8; H, 4.6; N, 29.0%]; m/z (EI) 242 (M þ 1)þ
100%, 241 (M)þ 2.8%, 215 (M-CN)þ 40.9%, 136 [(M þ 1)-C4H2N4]þ 4.9%,
124 [(M þ )-C5H2N4]þ 44.9%, 108 [(M þ 1)-C5H4N5]þ 4.3%; ꢀH (300 MHZ,
d6-DMSO) 3.78 (s, 3H, OCH3), 6.40 (br.s, 2H, NH2), 6.92 (d, 2H, 3J8,7 8 Hz,
H8 & H10), 7.42–7.90 (br. complex m, 3H, H7, H11 & H5), 9.90 (br.s, 1H,
NH) ppm; ꢀC (75 MHz, d6-DMSO) 59.1 (C12), 109.0 (C1), 118.1 (C8 &
C10), 118.8 and 119.9 (C3 & C4), 122.3 (C2), 124.5 (C7 & C11), 136.6
(C6), 150.9 (C5), 159.1 (C9) ppm; ꢁmax (Nujol mull) 3470 w, 3450 s, 3345
s, 3300 m, 3250 s, 3120 m (NH str.), 2215 s (CN str.), 2195 s (CN str.), 1650
m (C¼N str.), 1600 m (NH bend), 1575 w, 1515 m, 1310 s, 1290 m, 1245 s,
1220 s, 1175 m, 1030 s, 960 w, 820 s, 785 s cmꢀ1
.
REFERENCES
1. Booth, B.L.; Alves, M.J.; Proenca, M.F.J.R.P. J. Chem. Soc., Perkin
Trans. 1 1990, 1705.
2. Voet, A.B.; Schwartz, A.W. Bioorg. Chem. 1983, 12, 8.
3. Neilson, D.G. In The Chemistry of Amidines and Imidates; Wiley:
London, 1975; p. 1.
4. Shriner, R.L.; Neumann, F.W. Chem. Rev. 1944, 35, 351.
5. Booth, B.L.; Alves, M.J.; Proenca, M.F.J.R.P. J. Chem. Soc., Perkin
Trans. 1 1992, 913.
6. Alves, M.J.; Booth, B.L.; Al-Duaij, O.Kh.; Eastwood, P.R.; Nezhat, L.;
Proenca, M.F.J.R.P.; Ramos, A.S. J. Chem. Research (S) 1993, 402;
J. Chem. Research (M) 1993, 2701.

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3246
YAHYA-ZADEH AND BOOTH
7. Yahyazadeh, A.; Booth, B.L. Synth. Commun. 2001, 31(21), 19.
8. Booth, B.L.; Alves, M.J.; Carvalho, A.; Eastwood, P.R.; Nezhat, L.
J. Chem. Soc., Perkin Trans. 2 1994, 1949.
9. Woodward, D.W. U.S. Patent 2 534 331/1950.
Received in the UK April 20, 2001