Acta Chim. Slov. 2005, 52, 171–173
171
Short Communication
Synthesis of 3-[(2-Amino-l,2-dicyanovinyl)amino]-2-(benzoylamino)propenoates
Tomaž Trček and Bojan Verček*
Faculty of Chemistij and Chemical Technology, University of Ljubljana, Aškerčeva 5, 1000 Ljubljana, Slovenia;
E-mail: bojan.vercek@fkkt.uni-lj.si
Received 20-01-2005
Abstract
Two simple methods for the preparation of 3-[(2-amino-l,2-dicyanovinyl)amino]-2-(benzoyl amino)propenoates I   starting from 4-ethoxymethylidene-2-phenyl-5(4/f)-oxazolone and diaminomaleonitrile are described.
I   Key words: diaminomaleonitrile, 5(4/f)-oxazolones, propenoates
Introduction
Diaminomaleonitrile (DAMN) is an excellent synthetic tool for the preparation of highly substituted imidazoles, pyrimidines, pyrazines, purines, diazepines, pyrroles and other heterocycles.1,2 These syntheses are usually carried out via iV-substituted DAMN derivatives such as, for example, A^-(2-amino-l,2-dicyanovinyl) substituted form imidates, formamidines, formamid-razones, carboxamides, formamide 0-alkyloximes and Schiff bases. During the course of our investigations on the use of DAMN in heterocyclic synthesis, we designed new approaches to l,2,3-triazolyl substituted amino acid derivatives,3 imidazo[l,5-a]pyrazines,4 [l,2,3] triazolo[l,5-a]pyrazines,5 and [l,2,3] triazolo[l,5-a][l,2,4]triazolo [5,l-c] pyrazines.6 In some of these cases, new DAMN derivatives, alkyl 3-[(2-amino-l,2-dicyano vinyl)amino]-2-(benzoy l amino) propenoates, were used as the key intermediates. Since until now the preparation and characterization of the above stated propenoates have been mentioned only briefly, we give herein a report on these compounds in more detail.
Results and discussion
We have elaborated two simple general methods for the preparation of the propenoates 3 starting from the oxazolones 1 and 2 (Scheme 1, Table 1).
In the first one-pot approach, a mixture of 4-ethoxymethylidene-2-phenyl-5(4//)-oxazolone l,7 DAMN and the corresponding alcohol was heated under reflux to give the propenoates 3a-g in 23-82 % isolated yield. In the second approach, the iV-substituted DAMN 23 was heated in the corresponding alcohol
EtO ¦"^V\
o
Ph
DAMN / EtOH^ rt
NC H2N
CN
O
O
Ph
DAMN/ROH
A
ROH
A
NC H2N
CN
X.
NH  "^
^
COOR
NHCOPh
	R
a	methyl
b	ethyl
C	propyl
d	isopropyl
e	isobutyl
f	pentyl
g	cyclohexyl
Scheme 1. Synthesis of the propenoates 3a-g.
Table 1. Reaction times and yields in the synthesis of the propenoates 3a-g.
R	Product	Froml		From 2	
		Time	Yield<*	Time	YiekT'4
Methyl	3a	30 h	71	10 h	72
Efhyl	3b	9h	82 (733)	6h	79
Propyl	3c	1.5 h	55	1.5 h	71
Isopropyl	3d	23 h	35	8.5 h	58
Isobutyl	3e	2.5 h	23	50 min	70
Penryl	3f	5 min	37	11 min	68
Cyclohexyl	3g	6 min	26	2 min	51
' Refers to isolated percent yield.
O
1
3
Trček and Verček     Synthesis of 2-(Benzoylamino)propenoates
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Acta Chim. Slov. 2005, 52, 171–173
under reflux to afford the propenoates 3a-g in 51-79 % isolated yield. In order to avoid possible side trans-formations of these multifunctional starting compounds and products, and to obtain sufficiently pure products vvithout any additional purification, the reactions were performed in the absence of acid or base catalysts.
As evident from Table 1, the first one-pot procedure with 1 gave in most cases lower yields than the oxazolone ring opening of 2 probabh/ due to the decomposition of DAMN at higher tempera-tures. The shortest reaction times were observed in both procedures with alcohols having much higher boiling points (pentyl alcohol, cyclohexyl alcohol).
The propenoates 3 have Z,Z configuration on the carbon-carbon double bonds in the vinylamino-propenoate unit. It is known that DAMN (Z isomer) is more stable than diaminofumaronitrile (E isomer) and that during the N-substitution reactions carried out on one amino group of DAMN the configura-tional integrity is maintained.1'2 The Z configuration in the propenoate unit was established on the basis of the magnitude of the long-range heteronuclear coupling constant betvveen the carbonyl carbon and the methylidene proton for 3c (3Jc_H = 3 Hz) meas-ured from the antiphase splitting of cross peaks in the HMBC spectrum. 2D NMR spectroscopy was also used for the partial assignment of 13C signals for 3b.
Experimental
Melting points were determined on a Kofler micro hot stage and are uncorrected. NMR spectra were re-corded on a Bruker AVANCE DPX-300 spectrometer with TMS as an internal standard. Elemental analyses for C,H,N were obtained on a Perkin-Elmer CHN Ana-lyzer 2400. IR spectra were recorded on a Perkin-Elmer 1310 or 727 B spectrophotometer. MS spectra were obtained on a VG-Analytical AutoSpec Q instrument. Compounds l7 and 23 were prepared as described in the literature. Ali other compounds were used without purification as obtained from commercial sources.
General procedure for the preparation of the propenoates 3 from 1. A mixture of the oxazolone 1 (1 mmol), DAMN (1 mmol), and the corresponding alcohol (3 mL) was heated under reflux until the starting compounds disappeared (TLC monitoring). In the čase of 3b the reaction was carried out with 10 mmol of the oxazolone 1 and DAMN in 75 mL of ethanol. After cooling, the precipitated 3 was filtered off and washed with a small amount of the applied alcohol or ethanol.
General procedure for the preparation of the propenoates 3 from 2. A mixture of the oxazolone 2 (3 mmol in the cases of 3a, 3f, and 3g; 2 mmol in the cases of 3b, 3c, 3d, and 3e) and the corresponding alcohol (30 mL in the cases of 3a-f; 10 mL in the čase of 3g)
was heated under reflux until the starting compound disappeared (TLC monitoring). After cooling, the precipitated propenoate 3 was filtered off and washed with a small amount of the applied alcohol or ethanol.
Methyl (2Z)-3-{[(Z)-2-amino-l,2-dicyano-vinyl]amino}-2-(benzoylamino) propenoate (3a). mp 209-210 °C (EtOH). IR (KBr) v 3350, 3320, 3190, 2220, 2190, 1630, 1610, 1455, 1430, 1250, 700 cm"1. JH NMR (300 MHz, DMSO-d6) 5 3.63 (s, 3H, OCH3), 6.97 (s, 2H, NH2), 7.38 (d, J 12.2 Hz, 1H, H-3), 7.53 (m, 3H, H-3", H-4", H-5"), 7.95 (m, 3H, H-2", H-6", NH), 9.21 (s, 1H, NHCO). 13C NMR (75.5 MHz, DMSO-d6) 8 51.3, 96.9, 103.5, 114.8, 115.8, 118.7, 127.9, 128.2, 131.5, 134.0, 137.1, 165.3, 165.4. MS m/z (relative in-tensity): 311 (M+, 17). Anal. Calcd for C15H13N503: C 57.87, H 4.21, N 22.50. Found: C 58.19, H 4.05, N 22.56.
Ethyl (2Z)-3-{[(Z)-2-amino-l,2-dicyano-vinyl]amino}-2-(benzoylamino) propenoate (3b). mp 215-216 °C (EtOH) (lit.3 212.5-214.5 °C). 13C NMR (75.5 MHz, DMSO-d6) 5 14.3 (CH3), 59.7 (OCH2), 96.9 (C-l’), 103.7 (C-2), 114.7 (CN), 115.8 (CN), 118.7 (C-2’), 127.8 (C-2", C-6"), 128.1 (C-3", C-5"), 131.4 (C-4"), 134.0 (C-l"), 136.8 (C-3), 164.8 (C-l), 165.3 (NHCO). MS m/z (relative intensity): 325 (M+, 15).
Propyl (2Z)-3-{[(Z)-2-amino-l,2-dicyano-vinyl]amino}-2-(benzoylamino) propenoate (3c). mp 200-202 °C (PrOH). IR (KBr) v 3370, 3350, 3200, 2220, 2200, 1630, 1610, 1570, 1495, 1465, 1375, 1360, 1255, 1150, 705 cm"1. *H NMR (300 MHz, DMSO-d6) 8 0.88 (t, J 7.1 Hz, 3H, CH3), 1.58 (tq, J 6.8, 7.1 Hz, 2H, OCH,CH,,), 4.01 (t, J 6.8 Hz, 2H, OCH2), 6.95 (s, 2H, NH2), 7.39 (d, J 12.0 Hz, 1H, H-3), 7.53 (m, 3H, H-3", H-4", H-5"), 7.95 (m, 3H, H-2", H-6", NH), 9.19 (s, 1H, NHCO). 13C NMR (75.5 MHz, DMSO-d6) 8 10.3, 21.7, 65.1, 97.0, 103.7, 114.8, 115.7, 118.3, 127.8, 128.1,
131.4,  134.1, 136.7, 164.9, 165.4. MS m/z (relative in-tensity): 339 (M+, 16). Anal. Calcd for C17H17N503: C 60.17, H 5.05, N 20.64. Found: C 60.19, H 5.23, N 20.35.
Isopropyl (2Z)-3-{[(Z)-2-amino-l,2-dicyano vinyl]amino}-2-(benzoylamino) prop en oate (3d). mp 196-197 °C (i-PrOH). IR (KBr) v 3380, 3350, 3200, 2220, 2210, 1650, 1610, 1500, 1465, 1365, 1255, 1100, 705 cm"1. *H NMR (300 MHz, DMSO-d6) 8 1.21 (d, J 6.2 Hz, 6H, 2 CH3), 4.91 (septet, J 6.2 Hz, 1H, OCH), 6.96 (s, 2H, NH2), 7.34 (d, J 12.2 Hz, 1H, H-3), 7.52 (m, 3H, H-3", H-4", H-5"), 7.88 (d, J 12.2 Hz, 1H, NH), 7.96 (m, 2H, H-2", H-6"), 9.16 (s, 1H, NHCO). 13C NMR (75.5 MHz, DMSO-d6) 8 21.8, 66.9, 96.9, 104.1, 114.8, 115.8, 118.6, 127.8, 128.1, 131.4, 134.1,
136.5,  164.4, 165.3. MS-FAB m/z (relative intensity): 340 (MH+, 12). Anal. Calcd for C17H17N503: C 60.17, H 5.05, N 20.64. Found: C 60.31, H 5.04, N 20.67.
Isobutyl (2Z)-3-{[(Z)-2-amino-l,2-dicyano-vinyl]amino}-2-(benzoylamino) propen oate (3e). mp 201-203 °C (i-BuOH). IR (KBr) v 3370, 3350, 3200,
Trček and Verček     Sjmthesis of 2-(Benzoylamino)propenoates
Acta Chim. Slov. 2005, 52, 171–173
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2220, 2200, 1635, 1610, 1460, 1365, 1255, 1150, 700 cm"1. *H NMR (300 MHz, DMSO-d6) 5 0.88 (d, / 6.4 Hz, 6H, 2CH3), 1.86 (m, 1H, OCH2CH), 3.84 (d, / 6.4 Hz, 2H, OCH2), 6.94 (s, 2H, NH2), 7.42 (d, / 12.0 Hz, 1H, H-3), 7.53 (m, 3H, H-3", H-4", H-5"), 7.97 (m, 3H, H-2", H-6", NH), 9.18 (s, 1H, NHCO). 13C NMR (75.5 MHz, DMSO-d6) 5 18.9, 27.5, 69.5, 97.1, 103.7, 114.8, 115.7, 118.0, 127.8, 128.1, 131.4, 134.1, 136.7, 164.8, 165.5. MS miz (relative intensity): 353 (M+, 17). Anal. Calcd for C18H19N503: C 61.18, H 5.42, N 19.82. Found: C 60.80, H 5.69, N 19.43.
Pentyl (2Z)-3-{[(Z)-2-amino-l,2-dicyano-vinyl]amino}-2-(benzoylamino) propenoate (3f). mp 186-187 °C (EtOH). IR (KBr) v 3370, 3330, 3200, 2220, 2200, 1635, 1610, 1465, 1375, 1255, 1150, 705 cm"1. *H NMR (300 MHz, DMSO-d6) 5 0.83 (t, / 7.0 Hz, 3H, CH3), 1.28 (m, 4H, 2CH2), 1.55 (m, 2H, OCH2CH2), 4.04 (t,/6.4 Hz, 2H, OCH2), 6.95 (s, 2H, NH2), 7.38 (d, / 12.3 Hz, 1H, C-3), 7.53 (m, 3H, H-3", H-4", H-5"), 7.95 (m, 3H, H-2", H-6", NH), 9.18 (s, 1H, NHCO). 13C NMR (75.5 MHz, DMSO-d6) 5 13.8, 21.7, 27.6, 28.0, 63.6, 97.1, 103.7, 114.8, 115.7, 118.2, 127.8, 128.1, 131.4, 134.1, 136.7, 164.9, 165.4. MS miz (relative in-tensitv): 367 (M+, 17). Anal. Calcd for C19H21N503: C 62.11, H 5.76, N 19.06. Found: C 62.07, H 5.79, N 19.12.
Cyclohexyl (2Z)-3-{[(Z)-2-amino-l,2-dicyano-vinyl]amino}-2-(benzoylamino) prop en oate (3g). mp 182-183 °C (EtOH). IR (KBr) v 3380, 3340, 3200, 2920, 2230, 2210, 1655, 1615, 1505, 1475, 1365, 1255, 705 cm"1. JH NMR (300 MHz, DMSO-d6) 5 1.0-1.8
(m, 10H, cyclohexyl), 4.73 (m, 1H, cyclohexyl), 6.94 (s, 2H, NH2), 7.39 (d, /12.1 Hz, 1H, H-3), 7.53 (m, 3H, H-3", H-4", H-5"), 7.94 (m, 3H, H-2", H-6", NH), 9.16 (s, 1H, NHCO). 13C NMR (75.5 MHz, DMSO-d6) 5 22.7, 25.0, 31.0, 71.1, 97.1, 104.1, 114.8, 115.7, 118.1, 127.8, 128.1, 131.4, 134.2, 136.5, 164.2, 165.5. MS m/z (relative intensitv): 379 (M+, 8). Anal. Calcd for C20H21N5O3: C 63.31, H 5.58, N 18.46. Found: C 63.20, H 5.57, N 18.46.
Acknowledgements
This work was supported by the Ministry of Edu-cation, Science and Šport of Slovenia (P0-0503-0103, Pl-0230-0103).
References
1.  A. W. Erian, Chem. Rev. 1993, 93, 1991-2005, and references cited therein.
2.  A. Al-Azmi, A.-Z. A. Elassar, B. L. Booth, Tetrahedron 2003, 59, 2749-2763, and references cited therein.
3.  M. Polak, B. Verček, Synth. Commun. 2000, 30, 2863-2871.
4.   T. Trček, A. Meden, B. Verček, Synlett 2000, 1458-1460.
5.   T. Jug, M. Polak, T. Trček, B. Verček, Heterocycles 2002, 56, 353-360.
6.   T. Trček, B. Verček, ARKIVOC 2003, Part xiv, 246-252.
7.  J. W. Cornforth, The Chemistry of Penicillin; Princeton University Press, Princeton, 1949, p 803.
Povzetek
Opisani sta dve enostavni splošni metodi za pripravo 3-[(2-amino-1,2-dicianovinil) amino]-2-(benzoilamino)pro penoatov iz 4-etoksimetiliden-2-fenil-5(4H)-oksazolona in diamino maleo nitrila (DAMN).

Trček and Verček     Synthesis of 2-(Benzoylamino)propenoates