Synlett 2018; 29(09): 1157-1160
DOI: 10.1055/s-0036-1591962
letter
© Georg Thieme Verlag Stuttgart · New York

A New Simple Procedure for the Synthesis of Heptamethyl Cyclohepta-1,3,5-triene-1,2,3,4,5,6,7-heptacarboxylate

Alexander Yu. Belyy
a  N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, 47 Leninsky prosp., 119991 Moscow, Russian Federation   Email: [email protected]
,
Dmitry N. Platonov
a  N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, 47 Leninsky prosp., 119991 Moscow, Russian Federation   Email: [email protected]
,
Rinat F. Salikov
a  N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, 47 Leninsky prosp., 119991 Moscow, Russian Federation   Email: [email protected]
,
Anastasiya A. Levina
b  Higher Chemical College of the Russian Academy of Sciences, 9 Miusskaya sq., 125047 Moscow, Russian Federation
,
Yury V. Tomilov*
a  N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, 47 Leninsky prosp., 119991 Moscow, Russian Federation   Email: [email protected]
› Author Affiliations
Further Information

Publication History

Received: 10 January 2018

Accepted after revision: 23 February 2018

Publication Date:
22 March 2018 (online)


Abstract

A new and simple procedure for the synthesis of heptamethyl cyclohepta-1,3,5-triene-1,2,3,4,5,6,7-heptacarboxylate in a 51% yield is presented. An optimization of the reaction conditions was performed, and a convenient protocol for the isolation of the reaction product was developed. The structure of the key electrophilic intermediate was determined by means of NMR spectroscopy, and a plausible reaction mechanism is proposed.

 
  • References and Notes

  • 1 Tomilov YuV. Platonov DN. Salikov RF. Okonnishnikova GP. Tetrahedron 2008; 64: 10201
    • 2a Tomilov YuV. Platonov DN. Okonnishnikova GP. Tetrahedron Lett. 2009; 50: 5605
    • 2b Platonov DN. Okonnishnikova GP. Tomilov YuV. Mendeleev Commun. 2010; 20: 83
    • 2c Tomilov YuV. Platonov DN. Shulishov EV. Okonnishnikova GP. Levina AA. Tetrahedron 2015; 71: 1403
    • 2d Platonov DN. Okonnishnikova GP. Novikov RA. Suponitsky KYu. Tomilov YuV. Tetrahedron Lett. 2014; 55: 2381
    • 2e Tomilov YuV. Platonov DN. Okonnishnikova GP. Nefedov OM. Russ. Chem. Bull. 2010; 59: 1387
    • 2f Tomilov YV. Platonov DN. Shulishov EV. Okonnishnikova GP. Tetrahedron 2015; 69: 6855
  • 3 HMCH: General Procedure To a suspension of 1-(2-methoxy-2-oxoethyl)pyridinium bromide (3; 1.65 g, 7.1 mmol) and dimethyl bromomaleate (1; 5 g, 22.4 mmol) in the requisite volume of solvent (see Table 1) was added the requisite amount of pyridine, and the mixture was stirred for 72 h. In Method A (Table 1), the mixture was diluted with H2O (50 mL) and extracted with CHCl3 (3 × 25 mL). The combined organic phases were washed with 1 M NaHSO4 and brine, then dried (Na2SO4) and concentrated in vacuo. The residue was purified by column chromatography [silica gel, EtOAc–CHCl3 (1:4)]. In Method B, the mixture was poured into H2O (100 mL) with vigorous stirring. The mixture was filtered and the collected solid was washed with H2O and Et2O then dried in air.
  • 4 HMCH; Optimized Procedure To a suspension of 1-(2-methoxy-2-oxoethyl)pyridinium bromide (3; 16.4 g, 71 mmol) in DMF (36 mL) were added dimethyl 2,3-dibromosuccinate (64.4 g, 213 mmol) and pyridine (35.3g, 450 mmol), and the mixture was stirred for 72 h. The mixture was then poured into H2O (750 mL) with vigorous stirring and filtered. The collected solid was washed with H2O and Et2O, then dried in air to give a pale-purple powder; yield: 17.46 g (49%); mp 136–137 °C. 1H NMR (300 MHz, CDCl3): δ = 5.19 (s, 1 H), 3.84 (s, 6 H), 3.81 (s, 6 H), 3.80 (s, 6 H), 3.63 (s, 3 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 166.8 (2COO), 164.6 (COO), 164.5, 164.0 (2 × 2COO), 136.8, 133.7, 132.2 (3 × 2C), 53.4, 53.3 (2 × 2OCH3), 53.1 (OCH3), 53.0 (2OCH3), 43.4 (CH).
  • 5 1-[3-Methoxy-1-(methoxycarbonyl)-3-oxoprop-1-en-1-yl]pyridinium Bromide (4) The experiments were carried out in an NMR tube. (A) Pyridine (17 mg, 0.22 mmol) was added to a solution of dimethyl bromomaleate (1; 50 mg, 0.22 mmol) in DMSO-d 6 (0.5 mL), and the mixture was kept at rt. After 2 weeks, the conversion was 26%. (B) DMAD (44 mg, 0.31 mmol) was added to a solution of pyridine hydrobromide (50 mg, 0.31 mmol) in DMSO-d 6 (0.5mL), and the mixture was allowed to stand overnight. The yield was estimated to be ~90%. 1H NMR (300 MHz, DMSO-d 6): δ = 9.25 (dd, J = 6.7, 1.4 Hz, 2 H), 8.88 (tt, J = 7.9, 1.4 Hz, 1 H), 8.40–8.32 (m, 2 H), 7.48 (s, 1 H), 3.84 (s, 3 H), 3.61 (s, 3 H). 13C NMR (75 MHz, DMSO-d 6): δ = 162.3, 160.8, 149.3, 146.3, 139.9, 128.8, 128.2, 54.7, 53.4.
  • 6 4-Methoxy-1-(2-methoxy-2-oxoethyl)pyridinium Bromide (9a) Methyl bromoacetate (1.4 g, 9.17 mmol) was added to a solution of 4-methoxypyridine (1.0 g, 9.17 mmol) in acetone (4 mL). The mixture was stirred at rt for 24 h then filtered, washed with Et2O, and dried under reduced pressure to give a white solid; yield: 1.92 g (80%); mp 120–122 °C. 1H NMR (300 MHz, DMSO-d 6): δ = 8.92 (d, J = 7.3 Hz, 2 H), 7.74 (d, J = 7.4 Hz, 2 H), 5.61 (s, 2 H), 4.12 (s, 3 H), 3.74 (s, 3 H). 13C NMR (75 MHz, DMSO-d 6): δ = 171.7, 167.8, 147.9, 113.7, 58.9, 58.8, 53.5. HRMS (ESI+): m/z [M – Br]+ calcd for C9H12NO3: 182.0812; found: 182.0819.
  • 7 4-(2-Methoxy-2-oxoethyl)-1-methyl-1H-1,2,4-triazol-4-ium bromide (9b) Methyl bromoacetate (9.21 g, 60.2 mmol) was added to 1-methyl-1,2,4-triazole (9.21 g, 60.2 mmol), and the mixture was left for 3 d to give a white solid: yield: quant; mp 111–113 °C. 1H NMR (300 MHz, DMSO-d 6): δ = 10.22 (s, 1 H), 9.28 (s, 1 H), 5.46 (s, 2 H, CH2), 4.18 (s, 3 H, NMe), 3.79 (s, 3 H, COOMe). 13C NMR (75.5 MHz, CDCl3): δ = 166.1, 144.8, 143.1, 52.6, 47.6, 38.4. HRMS (ESI+): m/z [M – Br]+ calcd for C6H10N3O2: 156.0768; found: 156.0773.
  • 8 2-(2-Methoxy-2-oxoethyl)-1-methyl-1H-pyrazol-2-ium Bromide (9c) Methyl bromoacetate (10.7g, 65.7 mmol) was added to 1-methyl-1H-pyrazole (5.0 g, 65.7 mmol), and the mixture was left for 2 weeks to give a white solid; yield: quant; mp 104–107 °C. 1H NMR (300 MHz, DMSO-d 6): δ = 8.75 (d, 3 J = 1.2 Hz, 1 H), 8.66 (d, 3 J = 1.35 Hz, 1 H), 6.97 (dd, 3 J = 1.2, 1.35 Hz, 1 H), 5.82 (s, 2 H, CH2), 4.17 (s, 3 H, NMe), 3.79 (s, 3 H, COOMe). 13C NMR (75.5 MHz, DMSO-d 6): δ = 165.4 (COO), 138.5 (CH), 138.4 (CH), 107.0 (CH), 52.7, 49.5, 36.3. HRMS (ESI +): m/z [M – Br]+ calcd for C7H11N2O2: 155.0815; found: 155.0812
  • 9 1-(2-Oxopropyl)pyridinium bromide (10c), 1-(2-oxo-2-phenylethyl)pyridinium bromide (10b), 1-(2 methoxy-2-oxoethyl)pyridinium bromide (3)10, (cyanomethyl)(triethyl)ammonium chloride (10e)11, and 3-(2-methoxy-2-oxoethyl)-1-methyl-1H-imidazol-3-ium bromide (10f)12 were prepared according to the reported methods.
  • 10 Brioche J. Meyer C. Cossy J. Org. Lett. 2015; 17: 2800
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  • 13 Platonov DN. Belyy AYu. Ananyev IV. Tomilov YuV. Eur. J. Org. Chem. 2016; 4105