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Synlett 2017; 28(07): 858-862
DOI: 10.1055/s-0036-1588388
DOI: 10.1055/s-0036-1588388
letter
Synthesis of N-{5-Oxo-2-thioxo(2,5-dithioxo)hexahydroimidazo-[4,5-d]imidazol-1(2H)-yl}formamides
Further Information
Publication History
Received: 06 October 2016
Accepted after revision: 04 December 2016
Publication Date:
10 January 2017 (online)
![](https://www.thieme-connect.de/media/synlett/201707/lookinside/thumbnails/st-2016-d0667-l_10-1055_s-0036-1588388-1.jpg)
Abstract
A synthetic route to novel N-{5-oxo-2-thioxo(2,5-dithioxo)hexahydroimidazo[4,5-d]imidazol-1(2H)-yl}formamides, by a tandem N-formylation and ring-contraction reaction of 5,7-disubstituted 3-thioxoperhydroimidazo[4,5-e]-1,2,4-triazine-6-ones(thiones) with formic acid, has been developed.
Key words
N-heterocycles - thioanalogues of glycolurils - formylation - ring contraction - tandem reactionSupporting Information
- Supporting information for this article is available online at http://dx.doi.org/10.1055/s-0036-1588388.
- Supporting Information
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References and Notes
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- 23 Representative Analytical Data 7-Methyl-5-phenyl-3-thioxoperhydroimidazo[4,5-e]-1,2,4-triazin-6-one (1c) White solid; yield 0.537 g (51%); mp 258–260 °С (decomp.). 1H NMR (300 MHz, DMSO-d 6): δ = 2.73 (s, 3 H, Me), 5.02 (d, J = 8.5 Hz, 1 H, CH), 5.45–5.48 (dd, J = 8.5, 1.9 Hz, 1 H, CH), 5.86 (br s, 1 H, N(1)H), 7.13 (t, J = 7.2 Hz, 1 H, p-PhH), 7.35 (t, J = 7.8 Hz, 2 H, m-PhH), 7.48 (d, J = 8.1 Hz, 2 H, o-PhH), 8.62 (s, 1 H, N(4)H), 9.52 (s, 1 H, N(2)H). 13C NMR (75 MHz, DMSO-d 6): δ = 27.0, 62.1, 69.0, 122.0, 123.9, 128.6, 137.5, 155.8, 184.9. IR: 3208, 2971, 1698, 1595, 1529, 1500, 1477, 1439, 1396, 1303, 1261, 1147, 1120, 746. ESI-HRMS: m/z [M + H] calcd for C11H13N5OS: 264.0914; found: 264.0907. 7-Methyl-5-phenylperhydroimidazo[4,5-e]-1,2,4-triazin-3,6-dithione (1h) Yellowish solid; yield 0.514 (46%); mp 216–218 °С (decomp.). 1H NMR (500 MHz, DMSO-d 6): δ = 3.05 (s, 3 H, Me), 5.32–5.38 (m, 2 H, CH), 5.97 (s, 1 H, N(1)H), 7.30 (d, J = 7.6 Hz, 2 H, o-PhH), 7.33 (t, J = 7.4 Hz, 1 H, p-PhH), 7.42 (t, J = 7.6 Hz, 2 H, m-PhH), 8.70 (s, 1 H, N(4)H), 9.65 (s, 1 H, N(2)H). 13C NMR (75 MHz, DMSO-d 6): δ = 31.1, 66.7, 73.8, 127.2, 128.6, 129.1, 138.2, 181.1, 186.3. IR: 3177, 2959, 1595, 1554, 1500, 1407, 1388, 1335, 1293, 1265, 1213, 1136, 1108, 698. Anal. Calcd for C11H13N5S2: C, 47.29; H, 4.69; N, 25.07; S, 22.95. Found: C, 47.32; H, 4.70; N, 25.05; S, 22.91.
- 24 Synthesis of N-{4,6-Disubstituted 5-Oxo-2-thioxo(2,5-dithioxo)hexahydroimidazo[4,5-d]imidazol-1(2H)-yl}formamides 4a–i; General Procedure To a solution (or suspension) of imidazotriazine 1 (2 mmol) in acetone (22.5 mL) was added 90% formic acid (7.5 mL). The resulting mixture was heated to 55 °C and stirred for 2 h. Then the reaction mixture was cooled to r.t. and allowed to stand for 72 h to attain complete precipitation. The precipitate of compound 4 was filtered, washed with MeOH, and dried. Representative Analytical Data N-{4,6-Dimethyl-5-oxo-2-thioxohexahydroimidazo[4,5-d]-imidazol-1(2H)-yl}formamide (4a) White solid; yield 0.321 g (70%); mp 231–233 °С (decomp.). 1H NMR (300 MHz, DMSO-d 6): 70:30 (cis/trans): δ = 2.71 (s, 3 H, NMe), 2.78 (s, 2.1 H, NMe, cis), 2.81 (s, 0.9 H, NMe, trans), 5.34–5.45 (m, 2 H, CHCH), 8.08 (d, J = 10.5 Hz, 0.3 H, HCO, trans), 8.12 (s, 0.7 H, HCO, cis), 9.93 (s, 0.7 H, NH, cis), 9.97 (d, J = 10.5 Hz, 0.3 H, NNH, trans), 10.04 (s, 0.3 H, NH, trans), 10.52 (s, 0.7 H, NNH, cis). 13C NMR (75 MHz, DMSO-d 6): δ = 28.08 (NMe, trans), 28.12 (NMe, cis), 28.9 (NMe, cis), 29.6 (NMe, trans), 68.1 (CH, trans), 68.3 (CH, cis), 75.2 (CH, cis), 76.3 (CH, trans), 157.3 (CO, cis), 157.4 (CO, trans), 159.9 (HNCO, cis), 167.5 (HNCO, trans), 183.4 (CS, cis), 184.4 (CS, trans). IR: 3258, 2944, 2891, 1703, 1680, 1520, 1486, 1419, 1253, 1220, 1047, 754. ESI-HRMS: m/z [M + H] calcd for C7H11N5O2S: 230.0706; found: 230.0700. N-{4,6-Diethyl-5-oxo-2-thioxohexahydroimidazo[4,5-d]-imidazol-1(2H)-yl}formamide (4b) White solid; yield: 0.35 g (68%); mp 228–229 °С (decomp.). 1H NMR (300 MHz, DMSO-d 6): 70:30 (cis/trans): δ = 1.02–1.07 (m, 6 H, Me), 3.06–3.41 (m, 4 H, NCH2), 5.45–5.58 (m, 2 H, CHCH), 8.06 (d, J = 10.3 Hz, 0.3 H, HCO, trans), 8.13 (s, 0.7 H, HCO, cis), 9.94 (d, J = 10.3 Hz, 0.3 H, NNH, trans), 9.95 (s, 0.7 H, NH, cis), 10.05 (s, 0.3 H, NH, trans), 10.56 (s, 0.7 H, NNH, cis). 13C NMR (75 MHz, DMSO-d 6): δ = 12.76 (Me, trans), 12.86 (Me, cis), 12.92 (Me), 36.0 (NCH2), 36.6 (NCH2, cis), 37.0 (NCH2, trans), 66.5 (CH, trans), 66.6 (CH, cis), 73.2 (CH, cis), 74.2 (CH, trans), 156.8 (CO, cis), 157.0 (CO, trans), 160.2 (HNCO, cis), 167.8 (HNCO, trans), 183.7 (CS, cis), 184.6 (CS, trans). IR: 3200, 2988, 2973, 1709, 1677, 1539, 1501, 1470, 1436, 1252, 1229, 1068, 756. ESI-HRMS: m/z [M + H] calcd for C9H15N5O2S: 258.1019; found: 258.1021