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Synthesis of new derivatives of 2-imino-2,5-dihydrofurans

  • Aida Avetisyan and Lusine Karapetyan EMAIL logo
Published/Copyright: December 8, 2012
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Heterocyclic Communications
From the journal Heterocyclic Communications Volume 18 Issue 5-6

Abstract

New N-substituted 2-imino-2,5-dihydrofurans were synthesized by using several efficient approaches starting from readily available 2-imino-2,5-dihydrofurans. All new compounds were characterized by NMR and IR spectral data and elemental analysis.

Keywords: acidic hydrolysis; dimethyl sulfate; iminolactone; lactone; methyl iodide; N-nucleophile

Introduction

The 2-imino-2,5-dihydrofuran structure is related to 2-oxo-2,5-dihydrofuran fragment which constitutes a part of many natural molecules, in particular, ascorbic, penicillic and tetronic acids. Introduction of aromatic substituents into iminodihydrofuran molecules may be promising from the viewpoint of improving their biological activity (Avetisyan et al., 2011a,b) and other parameters, e.g., luminescent properties which are important for creation of optoelectronic materials (Hates et al., 2000).

Synthesis of new derivatives of 2-imino-2,5-dihydrofurans (Villemin and Liao, 2001, 2003; Avetissyan and Karapetyan, 2009; Avetisyan et al., 2009a,b, 2010, Avetisyan and Karapetyan, 2010; Cheikh et al., 2011) has been of continuous interest in the development of efficient and convenient methods for preparation of various 2,5-dihydrofuran derivatives and in their synthetic applications.

To determine new synthetic capabilities of 2-imino-2,5-dihydrofuran-3-carboxamides 1a–d (Avetissyan and Karapetyan, 2009), we studied the interaction of iminolactones with primary amines which is known in coumarin series (Zubkov et al., 1994; Gorobets et al., 2002; Shynkarenko et al., 2010). The reactions reported herein proceed under mild conditions, and the starting materials are readily available.

Results and discussion

The presence in these structures of the “iminolactone” ring, which may be regarded as a cyclic iminoester, led to the assumption that for these compounds there are possible transformations that resemble the reactions of iminoesters with N-nucleophiles (Roger and Neilson, 1961). However, interaction of 2-imino-2,5-dihydrofuran-3-carboxamides 1a–d with primary amines – aniline, p-toluidine, o-toluidine, phenylmethanamine in alcohols did not produce satisfactory results. By using instead of iminolactones 1a–d their hydrochlorides 2a–d, we obtained N-substituted 2-imino-2,5-dihydrofurans 3a–p in high yields (Scheme 1, route A).

Scheme 1
Scheme 1

The mechanism of the reaction of route A is similar to acidic hydrolysis of iminolactones to lactones which is essentially known in coumarin series (Houben and Pfankuch, 1926; Schiemenz, 1962). Formation of salts 2a–d leads to a significant increase in electrophilicity of the carbon atom of the imino group, and this atom then easily undergoes addition with an amine molecule. The intermediate formed is stabilized by the splitting off of the ammonium salt with the formation of N-substituted 2-imino-2,5-dihydrofurans 3a–p.

N-Substituted 2-imino-2,5-dihydrofurans 3a–t were also obtained by reaction of 2-imino-2,5-dihydrofuran-3-carboxamides 1a–d with hydrochlorides of primary amines – benzenaminium chloride, 4-methylbenzenaminium chloride, 2-methylbenzenaminium, phenylmethanaminium chloride, methanaminium chloride in ethanol (Scheme 1, route B). In this case, an equilibrium is apparently established between the base and the salt forms of 2-imino-2,5-dihydrofuran and amine, which leads to their mutual activation.

Formation of N-substituted 2-imino-2,5-dihydrofurans also takes place in the presence of sodium methoxide in methanol. Satisfactory results were obtained by route C only with aromatic amines, such as aniline, p-toluidine and o-toluidine. Compounds 3a–l were isolated after acidification of the solution.

2-(Methylimino)-2,5-dihydrofurans 3q–t were also obtained by reaction of 2-imino-2,5-dihydrofuran-3-carboxamides 1a–d with dimethyl sulfate in the presence of sodium carbonate (route D).

In continuation of our studies on the chemistry of 2-imino-2,5-dihydrofuran-3-carboxamides 1a–d, these compounds were allowed to react with methyl iodide in anhydrous acetone. The expected methylation to give products 4a,c was observed only with compounds 1a,c. Compounds 4a,c are readily hydrolyzed with aqueous hydrochloric acid (at pH 3–4) with the formation of 2,5-dihydrofuran-2-oxo-3-carboxamides 5a,c (Scheme 2). All compounds were characterized by spectroscopic methods.

Scheme 2
Scheme 2

Compounds 3a–t were tested for antibacterial activity at the chemotherapy laboratory, A. L. Mndzhoyan Institute of Fine Organic Chemistry, National Academy of Sciences of the Republic of Armenia. The test strains were Gram-positive Staphilococcus aureus (209p, 1, 93) and Gram-negative Shigella dysenteriae flexneri 6858, Escherichia coli 0–55. These compounds showed a moderate antibacterial activity in vitro, making it expedient to conduct further investigations in this area.

Experimental

All solvents were dried by standard methods. Melting points were measured with an Electrothermal 9100 apparatus. Elemental analyses were performed using a Heraeus CHN-O-Rapid analyzer. IR spectra were recorded on a Specord 75 IR spectrometer with samples dispersed in mineral oil. 1H NMR and 13C NMR spectra were recorded in DMSO-d6/CCl4 (1:3) solutions on a Varian Mercury-300 VX spectrometer at 300 and 75 MHz, respectively. The purity of synthesized compounds was tested by means of thin-layer chromatography (TLC) on Silufol UV-25 plates, eluent acetone/benzene (1:2), visualization with iodine vapors.

Compounds 1a–d and 2a–d were synthesized by using a published procedure (Avetissyan and Karapetyan, 2009).

General procedures for 3a–t

Route A

A mixture of 2a–d (2.5 mmol) and excess of an amine in anhydrous ethanol (10 mL) was heated under reflux for 15–20 min. The precipitate was filtered, washed with water and crystallized.

Route B

A mixture of 1a–d (2.5 mmol) and excess of an amine hydrochloride in anhydrous ethanol (10 mL) was heated under reflux for 30 min. The precipitate was filtered, washed with water and crystallized. The products were identical to compounds 3a–p (synthesized by route A) in melting points.

Route C

A mixture of 1a–d (2.5 mmol) and excess of an arylamine and sodium methoxide (0.058 g, 2.5 mmol) in anhydrous methanol (5 mL) was heated under reflux for 30 min. The mixture was cooled and acidified to pH 6 with 20% HCl. The precipitate was filtered, washed with water and crystallized. The products were identical to compounds 3a–l (synthesized by route A and by route B) in melting points.

Route D

To a solution of 1a–d (2 mmol) in dioxane (10 mL), conc. Na2CO3 solution (10 mL) and dimethyl sulfate (0.76 g, 6 mmol) were added. The mixture was stirred at room temperature for 5 h, then water (50 mL) was added and the stirring was continued for an additional 1 h. The precipitate was filtered, washed with water and crystallized. The products were identical to compounds 3q–t (synthesized by route B) in melting points.

4,5,5-Trimethyl-2-(phenylimino)-2,5-dihydrofuran-3-carboxamide (3a)

This compound was obtained as a white solid; yield 94% (route A), 95% (route B), 97% (route C); mp 172–173°C (from hexane); Rf = 0.56; IR: 1500–1602, 1621, 1641, 1682, 3120, 3300 cm-1; 1H NMR: δH 1.49 (s, 6H), 2.42 (s, 3H), 7,01 (tt, 1H, J = 7.3 Hz, J = 1.2 Hz), 7.12 (d, 2H), 7.24 (d, 2H), 7.32 (bs, 1H) and 8.88 (bs, 1H); 13C NMR: δC 11.8, 24.2, 87.6, 118.3, 122.3, 127.8, 130.4, 149.4, 162.3, 166,2, 170.8. Anal. Calcd for С14Н16N2О2: С, 68.83; Н, 6.60; N, 11.43. Found: С, 68.85; Н, 6.66; N, 11.44.

N,4,5,5-Tetramethyl-2-(phenylimino)-2,5-dihydrofuran-3-carboxamide (3b)

This compound was obtained as a pale yellow solid; yield 88% (route A), 89% (route B), 91% (route C); mp 99–101°C (from ethanol); Rf = 0.55; IR: 1500–1601, 1620, 1642, 1681, 3224 cm-1; 1H NMR: δH 1.49 (s, 6H), 2.42 (s, 3H), 2.82 (d, 3H, J = 4.9 Hz), 7.01 (tt, 1H, J = 7.3 Hz; J = 1.2 Hz), 7.12 (d, 2H), 7.24 (d, 2H), 9.88 (q, 1H, J = 7.6 Hz); 13C NMR: δC 11.8, 24.2, 41.7, 88.6, 118.3, 122.3, 127.8, 130.4, 149.4, 162.3, 166.2, 170.8. Anal. Calcd for С15Н18N2О2: С, 69.74; Н, 7.02; N, 10.84. Found: С, 69.75; Н, 7.04; N, 10.84.

(4-Methyl-2-(phenylimino)-1-oxaspiro[4.5]dec-3-ene-3-carboxamide (3c)

This compound was obtained as a white solid; yield 92% (route A), 95% (route B), 92% (route C); mp 208–209°C (from ethanol); Rf = 0.53; IR: 1501–1603, 1624, 1642, 1683, 3110, 3264 cm-1; 1H NMR: δH 1.27 (m, 1H), 1.47 (m, 2H) and 1.58–1.82 (m, 7H), 2.35 (s, 3H), 7.02 (tt, 1H, J = 7.3 Hz; J = 1.2 Hz), 7.12 (d, 2H), 7.24 (d, 2H), 7.32 (bs, 1H) and 8.88 (bs, 1H); 13C NMR: δC 12.1, 21.2, 23.9, 32.4, 88.7, 119.1, 122.3, 127.8, 130.4, 149.4, 162.4, 166.5, 170.9. Anal. Calcd for С17Н20N2О2: С, 71.80; Н, 7.09; N, 9.85. Found: С, 71.83; Н, 7.11; N, 9.86.

N,4-Dimethyl-2-(phenylimino)-1-oxaspiro[4.5]dec-3-ene-3-carboxamide (3d)

This compound was obtained as a pale yellow solid; yield 90% (route A), 89% (route B), 92% (route C); mp 123–124°C (from ethanol); Rf = 0.52; IR: 1502–1604, 1622, 1641, 1680, 3254 cm-1; 1H NMR: δH 1.27 (m, 1H), 1.47 (m, 2H) and 1.58–1.82 (m, 7H), 2.40 (s, 3H), 2.82 (d, 3H, J = 4.9 Hz), 7.01 (tt, 1H, J = 7.3 Hz, J = 1.2 Hz), 7.12 (d, 2H), 7.24 (d, 2H), 9.88 (q, 1H, J = 7.6 Hz); 13C NMR: δC 12.1, 21.2, 23.9, 32.4, 41.7, 88.7, 119.1, 122.3, 127.8, 130.4, 149.4, 162.4, 166.5, 170.9. Anal. Calcd for С18Н22N2О2: С, 72.46; Н, 7.43; N, 9.39. Found: С, 72.47; Н, 7.44; N, 9.40.

4,5,5-Trimethyl-2-(p-tolylimino)-2,5-dihydrofuran-3-carboxamide (3e)

This compound was obtained as a white solid; yield 95% (route A), 95% (route B), 97% (route C); mp 208–209°C (from ethanol); Rf = 0.55; IR: 1502–1605, 1621, 1644, 1681, 3124, 3224 cm-1; 1H NMR: δH 1.48 (s, 6H), 2.32 (s, 3H), 2.41 (s, 3H), 7.03 (s, 4H), 7.26 (bs, 1H) and 8.94 (bs, 1H); 13C NMR: δC 11.8, 20.3, 24.2, 87.6, 118.3, 122.3, 130.4, 136.9, 146.4, 162.3, 166.2, 170.8. Anal. Calcd for С15Н18N2О2: С, 69.74; Н, 7.02; N, 10.84. Found: С, 69.76; Н, 7.03; N, 10.86.

N,4,5,5-Tetramethyl-2-(p-tolylimino)-2,5-dihydrofuran-3-carboxamide (3f)

This compound was obtained as a pale yellow solid; yield 89% (route A), 87% (route B), 91% (route C); mp 108–109°C (from ethanol); Rf = 0.54; IR: 1502–1604, 1624, 1642, 1680, 3264 cm-1; 1H NMR: δH 1.48 (s, 6H), 2.28 (s, 3H), 2.42 (s, 3H), 2.82 (d, 3H, J = 4.9 Hz), 7.04 (s, 4H), 9.88 (q, 1H, J = 7.6 Hz); 13C NMR: δC 11.8, 20.3, 24.2, 41.6, 87.6, 118.3, 122.3, 130.4, 136.9, 146.4, 162.3, 166.2, 170.8. Anal. Calcd for С16Н120N2О2: С, 70.56; Н, 7.40; N, 10.29. Found: С, 70.58; Н, 7.43; N, 10.31.

4-Methyl-2-(p-tolylimino)-1-oxaspiro[4.5]dec-3-ene-3-carboxamide (3g)

This compound was obtained as a white solid; yield 92% (route A), 95% (route B), 92% (route C); mp 189–190°C (from benzene); Rf = 0.52; IR: 1504–1601, 1622, 1644, 1682, 3224, 3300 cm-1; 1H NMR: δH 1.27 (m, 1H), 1.47 (m, 2H) and 1.58–1.82 (m, 7H), 2.32(s, 3H), 2.42 (s, 3H), 7.04 (s, 4H), 7.26 (bs, 1H) and 8.94 (bs, 1H); 13C NMR: δC 11.8, 20.3, 21.2, 23.9, 32.4, 87.6, 118.3, 122.3, 130.4, 136.9, 146.4, 162.3, 166.2, 170.8. Anal. Calcd for С18Н22N2О2: С, 72.46; Н, 7.43; N, 9.39. Found: С, 72.48; Н, 7.44; N, 9.41.

N,4-Dimethyl-2-(p-tolylimino)-1-oxaspiro[4.5]dec-3-ene-3-carboxamide (3h)

This compound was obtained as a pale yellow solid; yield 91% (route A), 93% (route B), 92% (route C); mp 125–126°C (from hexane); Rf = 0.51; IR: 1501–1602, 1621, 1642, 1684, 3254 cm-1; 1H NMR: δH 1.27 (m, 1H), 1.47 (m, 2H) and 1.58–1.82 (m, 7H), 2.32 (s, 3H), 2.41 (s, 3H), 2.82 (d, 3H, J = 4.9 Hz), 7.04 (s, 4H), 9.86 (q, 1H, J = 7.6 Hz); 13C NMR: δC 11.8, 20.3, 21.2, 23.9, 32.4, 41.6, 87.7, 118.3, 122.3, 130.4, 136.9, 146.4, 162.3, 166.2, 170.8. Anal. Calcd for С19Н24N2О2: С, 73.05; Н, 7.74; N, 8.97. Found: С, 73.06; Н, 7.76; N, 8.99.

4,5,5-Trimethyl-2-(o-tolylimino)-2,5-dihydrofuran-3-carboxamide (3i)

This compound was obtained as a white solid; yield 94% (route A), 94% (route B), 95% (route C); mp 215–216°C (from ethanol); Rf = 0.54; IR: 1502–1602, 1624, 1640, 1681, 3124, 3250 cm-1; 1H NMR: δH 1.46 (s, 6H), 2.17 (s, 3H), 2.42 (s, 3H), 6.90 (td, 1H, J = 7.4 Hz, J = 1.4 Hz), 6.96 (dd, 1H, J = 8.0 Hz, J = 1.4 Hz), 7.05 (td, 1H, J = 7.4 Hz, J = 1.4 Hz), 7.09 (dd, 1H, J = 7.4 Hz, J = 1.4 Hz), 7.32 (bs, 1H) and 8.87 (bs, 1H); 13C NMR: δC 11.8, 18.4, 24.2, 87.6, 118.3, 120.3, 127.0, 127.1, 128.4, 130.4, 146.4, 162.3, 166.2, 170.8. Anal. Calcd for С15Н18N2О2: С, 69.74; Н, 7.02; N, 10.84. Found: С, 69.76; Н, 7.03; N, 10.86.

N,4,5,5-Tetramethyl-2-(o-tolylimino)-2,5-dihydrofuran-3-carboxamide (3j)

This compound was obtained as a pale yellow solid; yield 88% (route A), 88% (route B), 92% (route C); mp 85–86°C (from benzene); Rf = 0.53; IR: 1501–1604, 1620, 1642, 1681, 3275 cm-1; 1H NMR: δH 1.46 (s, 6H), 2.18 (s, 3H), 2.42 (s, 3H), 2.81 (d, 3H, J = 4.9 Hz), 6.91 (td, 1H, J = 7.4 Hz, J = 1.4 Hz), 6.96 (dd, 1H, J = 8.0 Hz, J = 1.4 Hz), 7.05 (td, 1H, J = 7.4 Hz, J = 1.4 Hz), 7.09 (dd, 1H, J = 7.4 Hz, J = 1.4 Hz), 9.86 (q, 1H, J = 7.6 Hz); 13C NMR: δC 11.8, 18.4, 24.2, 41.7, 87.6, 118.3, 120.3, 127.0, 127.1, 128.4, 130.4, 146.4, 162.3, 166.2, 170.8. Anal. Calcd for С16Н120N2О2: С, 70.56; Н, 7.40; N, 10.29. Found: С, 70.58; Н, 7.43; N, 10.31.

4-Methyl-2-(o-tolylimino)-1-oxaspiro[4.5]dec-3-ene-3-carboxamide (3k)

This compound was obtained as a white solid; yield 91% (route A), 92% (route B), 90% (route C); mp 192–193°C (from ethanol); Rf = 0.51; IR: 1501–1601, 1624, 1641, 1682, 3122, 3264 cm-1; 1H NMR: δH 1.27 (m, 1H), 1.47 (m, 2H) and 1.58–1.82 (m, 7H), 2.32 (s, 3H), 2.42 (s, 3H), 7.04 (s, 4H), 6.90 (td, 1H, J = 7.4 Hz, J = 1.4 Hz), 6.96 (dd, 1H, J = 8.0 Hz, J = 1.4 Hz), 7.04 (td, 1H, J = 7.4 Hz, J = 1.4 Hz), 7.09 (dd, 1H, J = 7.4 Hz, J = 1.4 Hz), 7.26 (bs, 1H) and 8.94 (bs, 1H); 13C NMR: δC 11.8, 18.4, 21.2, 23.9, 32.4, 87.6, 118.3, 120.3, 127.0, 127.1, 128.4, 130.4, 146.4, 162.3, 166.2, 170.8. Anal. Calcd for С18Н22N2О2: С, 72.46; Н, 7.43; N, 9.39. Found: С, 72.48; Н, 7.44; N, 9.41.

N,4-Dimethyl-2-(o-tolylimino)-1-oxaspiro[4.5]dec-3-ene-3-carboxamide (3l)

This compound was obtained as a pale yellow solid; yield 88% (route A), 87% (route B), 90% (route C); mp 113–114°C (from benzene); Rf = 0.50; IR: 1502–1602, 1621, 1640, 1680, 3274 cm-1; 1H NMR: δH 1.27 (m, 1H), 1.47 (m, 2H) and 1.58–1.82 (m, 7H), 2.32 (s, 3H), 2.41 (s, 3H), 2.82 (d, 3H, J = 4.9 Hz), 6.90 (td, 1H, J = 7.4 Hz, J = 1.4 Hz), 6.96 (dd, 1H, J = 8.0 Hz, J = 1.4 Hz), 7.04 (td, 1H, J = 7.4 Hz, J = 1.4 Hz), 7.09 (dd, 1H, J = 7.4 Hz, J = 1.4 Hz), 9.86 (q, 1H, J = 7.6 Hz); 13C NMR: δC 11.8, 18.4, 21.2, 23.9, 32.4, 41.6, 87.6, 118.3, 120.3, 127.0, 127.1, 128.4, 130.4, 146.4, 162.3, 166.2, 170.8. Anal. Calcd for С19Н24N2О2: С, 73.05; Н, 7.74; N, 8.97. Found: С, 73.06; Н, 7.76; N, 8.99.

2-(Benzylimino)-4,5,5-trimethyl-2,5-dihydrofuran-3-carboxamide (3m)

This compound was obtained as a white solid; yield 90% (route A), 91% (route B); mp 113–115°C (from toluene); Rf = 0.57; IR: 1502–1601, 1624, 1641, 1675, 3220, 3340 cm-1; 1H NMR: δH 1.46 (s, 6H), 2.37 (s, 3H), 4.51 (s, 2H), 7.17 (m, 1H) and 7.25–7.28 (m, 4H), 7.16 (bs, 1H) and 8.99 (bs, 1H); 13C NMR: δC 11.8, 24.2, 42.6, 87.6, 118.3, 125.3, 127.8, 128.4, 138.4, 160.4, 166.2, 170.8. Anal. Calcd for С15Н18N2О2: С, 69.74; Н, 7.02; N, 10.84. Found: С, 69.76; Н, 7.03; N, 10.86.

2-(Benzylimino)-N,4,5,5-tetramethyl-2,5-dihydrofuran-3-carboxamide (3n)

This compound was obtained as a pale yellow solid; yield 85% (route A), 87% (route B); mp 135–136°C (from ethanol); Rf = 0.56; IR: 1502–1604, 1622, 1640, 1681, 3220 cm-1; 1H NMR: δH 1.46 (s, 6H), 2.35 (s, 3H), 2.82 (d, 3H, J = 4.9 Hz), 4.51 (s, 2H), 7.17 (m, 1H) and 7.25–7.28 (m, 4H), 9.88 (q, 1H, J = 7.6 Hz); 13C NMR: δC 11.8, 24.2, 41.5, 42.6, 87.6, 118.3, 125.3, 127.8, 128.4, 138.4, 160.4, 166.2, 170.8. Anal. Calcd for С16Н120N2О2: С, 70.56; Н, 7.40; N, 10.29. Found: С, 70.57; Н, 7.42; N, 10.33.

2-(Benzylimino)-4-methyl-1-oxaspiro[4.5]dec-3-ene-3-carboxamide (3o)

This compound was obtained as a white solid; yield 92% (route A), 95% (route B); mp 142–143°C (from ethanol); Rf = 0.53; IR: 1502–1604, 1621, 1644, 1684, 3224, 3300 cm-1; 1H NMR: δH 1.27 (m, 1H), 1.47 (m, 2H) and 1.58–1.82 (m, 7H), 2.43 (s, 3H), 4.51 (s, 2H), 7.18 (m, 1H) and 7.25–7.28 (m, 4H), 7.32 (bs, 1H) and 8.88 (bs, 1H); 13C NMR: δC 11.8, 21.2, 23.9, 32.4, 42.6, 87.6, 118.3, 125.3, 127.8, 128.4, 138.4, 160.4, 166.2, 170.8. Anal. Calcd for С18Н22N2О2: С, 72.46; Н, 7.43; N, 9.39. Found: С, 72.47; Н, 7.45; N, 9.42.

2-(Benzylimino)-N,4-dimethyl-1-oxaspiro[4.5]dec-3-ene-3-carboxamide (3p)

This compound was obtained as a pale yellow solid; yield 91% (route A), 93% (route B); mp 85–86°C (from ethanol); Rf = 0.51; IR: 1501–1602, 1622, 1640, 1680, 3280 cm-1; 1H NMR: δH 1.27 (m, 1H), 1.47 (m, 2H) and 1.58–1.82 (m, 7H), 2.42 (s, 3H), 2.82 (d, 3H, J = 4.9 Hz), 4.52 (s, 2H), 7.18 (m, 1H) and 7.26–7.30 (m, 4H), 9.88 (q, 1H, J = 7.6 Hz); 13C NMR: δC 11.8, 21.2, 23.9, 32.4, 41.6, 42.6, 87.6, 118.3, 125.3, 127.8, 128.4, 138.4, 160.4, 166.2, 170.8. Anal. Calcd for С19Н24N2О2: С, 73.05; Н, 7.74; N, 8.97. Found: С, 73.07; Н, 7.74; N, 8.98.

4,5,5-Trimethyl-2-(methylimino)-2,5-dihydrofuran-3-carboxamide (3q)

This compound was obtained as a pale yellow solid; yield 89% (route B), 92% (route D); mp 180–182°C (from hexane); Rf = 0.55; IR: 1622, 1641, 1680, 3124, 3301 cm-1; 1H NMR: δH 1.42 (s, 6H), 2.35 (s, 3H), 2.98 (s, 3Н), 7.14 (bs, 1H) and 8.84 (bs, 1H); 13C NMR: δC 11.7, 12.5, 24.2, 87.3, 118.9, 162.3, 166.3, 170.9. Anal. Calcd for С9Н14N2О2: С, 59.32; Н, 7.74; N, 15.37. Found С, 59.35; Н, 7.76; N, 15.40.

N,4,5,5-Tetramethyl-2-(methylimino)-2,5-dihydrofuran-3-carboxamide (3r)

This compound was obtained as a pale yellow liquid; yield 86% (route B), 83% (route D); bp 118–120°C (6 mm Hg); nD20 1.5094; Rf = 0.54; IR: 1620, 1641, 1685, 3240 cm-1; 1H NMR: δH 1.42 (s, 6H), 2.35 (s, 3H), 2.82 (d, 3H, J = 4.9 Hz), 2.96 (s, 3Н), 9.88 (q, 1H, J = 7.6 Hz); 13C NMR: δC 11.8, 12.5, 24.2, 41.6, 87.3, 118.9, 162.3, 166.3, 170.9. Anal. Calcd for С10Н16N2О2: С, 61.20; Н, 8.22; N, 14.27. Found: С, 61.25; Н, 8.26; N, 14.30.

4-Methyl-2-(methylimino)-1-oxaspiro[4.5]dec-3-ene-3-carboxamide (3s)

This compound was obtained as a pale yellow solid; yield 89% (route B), 92% (route D); mp 207–208°C (from benzene); Rf = 0.52; IR: 1621, 1645, 1678, 3128, 3264 cm-1; 1H NMR: δH 1.27 (m, 1H), 1.47 (m, 2H) and 1.58–1.82 (m, 7H), 2.35 (s, 3H), 2.99 (s, 3Н); 7.14 (bs, 1H) and 8.84 (bs, 1H); 13C NMR: δC 12.1, 12.5, 21.2, 23.9, 32.4, 88.7, 119.1, 162.4, 166.4, 170.9. Anal. Calcd for С12Н18N2О2: С, 64.84; Н, 8.16; N, 12.60. Found: С, 64.85; Н, 8.18; N, 12.61.

N,4-Dimethyl-2-(methylimino)-1-oxaspiro[4.5]dec-3-ene-3-carboxamide (3t)

This compound was obtained as a pale yellow solid; yield 88% (route B), 93% (route D); mp 118–120°C (from ethanol); Rf = 0.51; IR: 1621, 1642, 1681, 3270 cm-1; 1H NMR: δH 1.27 (m, 1H), 1.47 (m, 2H) and 1.58–1.82 (m, 7H), 2.35 (s, 3H), 2.82 (d, 3H, J = 4.9 Hz), 2.96 (s, 3Н), 9.88 (q, 1H, J = 7.6 Hz); 13C NMR: δC 12.0, 12.5, 21.2, 23.9, 32.4, 41.6, 88.7, 119.1, 162.4, 166.4, 170.9. Anal. Calcd for С13Н20N2О2: С, 66.07; Н, 8.53; N, 11.85. Found: С, 66.09; Н, 8.58; N, 11.61.

General procedure for 4a,c

A mixture of 2a,c (2.5 mmol) and methyl iodide (0.2 mL, 3.75 mmol) in anhydrous acetone (10 mL) was stirred at room temperature for 20 h. The precipitated solid was filtered, washed with acetone and crystallized from ethanol or hexane.

N-(3-Carbamoyl-4,5,5-trimethylfuran-2(5H)-ylidene)methanaminium iodide (4a)

This compound was obtained as a white solid; yield 71%; mp 264–266°C (from ethanol); Rf = 0.57; IR: 1620, 1640, 1680, 3140, 3300 cm-1; 1H NMR: δH 1.42 (s, 6H), 2.35 (s, 3H), 2.98 (d, 3H, J = 4.9 Hz), 7.16 (bs, 1H) and 8.99 (bs, 1H), 10.70 (bs, 1H). Anal. Calcd for С9Н15N2О2J: С, 34.86; Н, 4.88; N, 9.03. Found: С, 34.88; Н, 4.89; N, 9.04.

N-(3-Carbamoyl-4-methyl-1-oxaspiro[4.5]dec-3-en-2-ylidene)methanaminium iodide (4c)

This compound was obtained as a white solid; yield 85%; mp 207–210°C (from hexane); Rf = 0.54; IR: 1620, 1640, 1680, 3300 cm-1; 1H NMR: δH 1.27 (m, 1H), 1.47 (m, 2H) and 1.58–1.82 (m, 7H), 2.35 (s, 3H), 2.99 (d, 3H, J = 4.9 Hz), 7.14 (bs, 1H) and 8.84 (bs, 1H), 10.70 (bs, 1H). Anal. Calcd for С12Н19N2О2J: С, 41.16; Н, 5.47; N, 8.00. Found С, 41.18; Н, 5.49; N, 8.02.

General procedure for 5a,c

A solution of 4a,c (2.5 mmol) in 10 mL of a mixture of ethanol/water/31% hydrochloric acid (30:1:1, v/v/v) was heated under reflux with vigorous stirring for 1 h, then cooled and extracted with diethyl ether (3×10 mL). The extract was dried with magnesium sulfate, concentrated and the residue was crystallized using a solvent indicated below.

4,5,5-Trimethyl-2-oxo-2,5-dihydrofuran-3-carboxamide (5a)

This compound was obtained as a white solid; yield 85%; mp 125–126°C (from petroleum ether) (Avetissyan and Karapetyan, 2009).

4-Methyl-2-oxo-1-oxaspiro[4.5]dec-3-ene-3-carboxamide (5c)

This compound was obtained as a white solid; yield 84%; mp 161–163°C (from octane) (Avetisyan et al., 1971).

Corresponding author: Lusine Karapetyan, Yerevan State University, Alex Manoogian 1, 0025, Yerevan, Armenia

We are grateful to Dr. Henrik Panosyan for NMR analyses (Molecular Structure Research Center, Yerevan, Armenia).

References

Avetissyan, A.; Karapetyan, L. The synthesis of new 2-iminoderivatives of 2,5-dihydrofurans and their chemical transformations. Synth. Commun. 2009, 39, 7–19.Search in Google Scholar

Avetisyan, A. A; Karapetyan, L. V. Synthesis of new heterocyclic derivatives of 2-imino-2,5-dihydrofurans and some of their chemical transformations. Chem. Heterocycl. Compd. (Engl. Transl.) 2010, 46, 15–19.Search in Google Scholar

Avetisyan, A. A.; Tatevosyan, G. E.; Dangyan, M. T. Investigations in the field of unsaturated lactones. The reaction of 3-carbethoxy-4-methyl-5,5-dialkyl-Δ3-butenolides with amines. Arm. Khim. Zh. 1971, 24, 688–693.Search in Google Scholar

Avetisyan, A. A.; Alvandzhyan, A. G.; Avetisyan, K. S. Synthesis of new 2-substituted 2,5-dihydrofuranone derivatives and their chemical transformations. Russ. J. Org. Chem. (Engl. Transl.) 2009a, 45, 1871–1872.10.1134/S1070428009120240Search in Google Scholar

Avetisyan, A. A; Karapetyan, L. V.; Tadevosyan, M. D. Synthesis of 2-imino-4-vinyl-2,5-dihydrofuran-3-carboxamides and some of their chemical transformations. Russ. J. Org. Chem. (Engl. Transl.) 2009b, 45, 1031–1035.10.1134/S1070428009070082Search in Google Scholar

Avetisyan, A. A.; Karapetyan, L. V.; Tadevosyan, M. D. Synthesis and chemical transformations of novel functionalized 2-imino-2,5-dihydrofurans. Russ. Chem. Bull. (Engl. Transl.) 2010, 59, 974–976.Search in Google Scholar

Avetisyan, A. A; Karapetyan, L. V.; Paronikyan, R. V.; Stepanyan, H. M. Synthesis and antibacterial activity of new 2,5-dihydrofuran derivatives. Pharm. Chem. J. (Engl. Transl.) 2011a, 45, 156–158.10.1007/s11094-011-0582-2Search in Google Scholar

Avetisyan, A. A; Karapetyan, L. V.; Paronikyan, R. V.; Stepanyan, H. M. Synthesis and antibacterial activity of 4-(2-R-vinyl) derivatives of functionally substituted 2,5-dihydrofurans. Pharm. Chem. J. (Engl. Transl.) 2011b, 45, 723–724.10.1007/s11094-012-0711-6Search in Google Scholar

Cheikh, N.; Bar, N.; Choukchou-Braham, N.; Mostefa-Kara, B.; Lohier, J. F.; Sopkova, J.; Villemin, D. Efficient synthesis of new butenolides by subsequent reactions: application for the synthesis of original iminolactones, bis-iminolactones and bis-lactones. Tetrahedron 2011, 67, 1540–1551.Search in Google Scholar

Gorobets, N. Yu.; Borisov, A. V.; Silin, A. V.; Nikitchenko, V. M.; Kovalenko, S. N. Reactions of 3-(4-aryl-3-thiazolyl)-and 3-(2-benzothiazolyl)-iminocoumarins with N-nucleophiles. Chem. Heterocycl. Compd. (Engl. Transl.) 2002, 38, 1389–1396.Search in Google Scholar

Hates, R. T.; Wasielevski, M. R.; Gosztola, D. Ultrafast photoswitched charge transmission through the bridge molecule in a donor-bridge-acceptor system. J. Am. Chem. Soc. 2000, 122, 5563–5567.Search in Google Scholar

Houben, J.; Pfankuch, E. Uber imino-lactone and salze ungesattigter nitrile. Chem. Ber. 1926, 59, 1594–1605.Search in Google Scholar

Roger, R.; Neilson, D. G. The chemistry of imidates. Chem. Rev. 1961, 61, 179–211.Search in Google Scholar

Schiemenz, G. P. Synthesen mit Cyanessigsäure, III. Zur Reaktion von 2-Hydroxy-benzaldehyd mit Cyanacetamid und Malodinitrilv. Chem. Ber. 1962, 2, 483–486.Search in Google Scholar

Shynkarenko, P. E.; Vlasov, S. V.; Kovalenko, S. M.; Chernykh, V. P. Recyclization of 2-iminocoumarin-3-carbonitriles with 2-aminothiobenzamide: a new synthetic route to substituted 2-(2-iminocoumarin-3-yl)qiunazoline-4(3H)-thioones). J. Sulfur Chem. 2010, 31, 447–456.Search in Google Scholar

Villemin, D.; Liao, L. Rapid and efficient synthesis of 2-[3-cyano-4-(2-aryliden)-5,5dimethyl-5H-furan-2-ylidene]malononitrile under focused microwave irradiation. Synth. Commun. 2001, 31, 1771–1780.Search in Google Scholar

Villemin, D.; Liao, L. Application of microwaves in organic synthesis: a rapid and efficient synthesis of new 3-aryl-2-imino-4-methyl-2,5-dihydrofurans and 3-aryl-3–2-(5H)-furanones. Synth. Commun. 2003, 33, 1575–1585.Search in Google Scholar

Zubkov, V. A.; Kovalenko, S. N.; Chernykh, V. P.; Ivkov, S. M. New derivatives of coumarin: 2-(N-R-imino)-2H-1-benzopyrans. Khim. Geterotsikl. Soedin. 1994, 30, 760–766.Search in Google Scholar

Received: 2012-7-31
Accepted: 2012-11-1
Published Online: 2012-12-08
Published in Print: 2012-12-01

©2012 by Walter de Gruyter Berlin Boston

This article is distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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https://doi.org/10.1515/hc-2012-0113
Keywords for this article
acidic hydrolysis; dimethyl sulfate; iminolactone; lactone; methyl iodide; N-nucleophile
Creative Commons
BY-NC-ND 3.0

Articles in the same Issue

  1. Masthead
  2. Masthead
  3. Research Articles
  4. Sequential amination of heteroaromatic halides with aminopyridine 1 - oxides and their N-protected derivatives based on novel aza-Smiles rearrangement
  5. Convenient synthetic route to 3-cyanopyridine-2(1H)-one derivatives with aromatic substituents
  6. Synthesis and antioxidant activity of a series of novel 3-chalcone-substituted 1,4-dihydropyridine derivatives
  7. An efficient one-pot multi-component synthesis of highly functionalized piperidines
  8. Scandium triflate-catalyzed one-pot multi-component synthesis of 2-amino-6-thiopyridine-3,5-dicarbonitriles
  9. Facile approach to the synthesis of substituted thieno[2,3-d]pyrimidin-4-ones
  10. Focused microwave-assisted efficient and convenient synthesis of new pyrido[2,3-d]pyrimidinone derivatives
  11. Synthesis of new derivatives of 2-imino-2,5-dihydrofurans
  12. Photooxidative cyclization of 3-aryl/heteroaryl-4-heteroaryl coumarins: an experimental and semi-empirical study
  13. Synthesis and antimicrobial activity of derivatives of 1H-benzo[de]isoquinoline-1,3(2H)-dione
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