Synthesis of Unsymmetrical Pyrrolo[3,2-b]pyrrole-2,5-diones

Abstract

The first unsymmetrical oxalic acid-bis(imidoyl)dichlorides were prepared and applied to the one-pot synthesis of the first unsymmetrical pyrrolo[3,2-b]pyrrole-2,5-diones and 2,2′-bis-quinazolin-4-ones.

Key words

one-pot synthesis - unsymmetrical pyrrolo[3,2-b]pyrrole-2,5-diones - dilactams of pulvinic acid

References

• 1a Closs F. Gompper R. Angew. Chem., Int. Ed. Engl.  1987,  26:  552 ; Angew. Chem. 1987, 99, 564
• 1b Closs F. Gompper R. Nöth H. Wagner H.-U. Angew. Chem., Int. Ed. Engl.  1988,  27:  842 ; Angew. Chem. 1988, 100, 875
• 1c Casser L, Iqbal A, and Rochat AC. inventors; Eur. Pat. Appl., EP  98808.  ; Ciba-Geigy
• 2a Beyerlein T. Tieke B. Macromol. Rapid Commun.  2000,  21:  182 
• 2b Beyerlein T. Tieke B. Forero-Lenger S. Brütting W. Synth. Metals  2002,  130:  115 
• 3a Rao YS. Chem. Rev.  1976,  76:  625 
• 3b Pattenden G. Prog. Chem. Nat. Prod.  1978,  35:  133 
• 3c Knight DW. Contemp. Org. Synth.  1994,  1:  287 
• 3d Schweppe M. Handbuch der Naturfarbstoffe   ecomed Verlagsgesellschaft; Landsberg: 1992.  p.185 
• 3e Schweppe M. Handbuch der Naturfarbstoffe   ecomed Verlagsgesellschaft; Landsberg: 1992.  p.525 
• 4 Herbst W. Hunger K. Industrial Organic Pigments   VCH; Weinheim: 1993.  p.550 
• Selected symmetrical pyrrolo[3,2-b]pyrrole-2,5-diones have been prepared in three steps from (N-phenylacetyl)-acetic acid amino ester:
• 5a Fürstenwerth H. inventors; Ger. Offen., DE  3,525,109 A1. Bayer AG, a one step synthesis using pulvinic acid proceeded under harsh conditions (autoclave reaction, 140-180 °C: ; Chem. Abstr. 1987, 106, 103815f
• 5b Rochat AC, Iqbal A, Pfenninger J, and Casser L. inventors; Eur. Pat. Appl., EP  016309. Ciba-Geigy:
• 5c See also: Solberg Y. Z. Naturforsch.  1977,  32c:  292 
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• 5e Mukai T. Konno A. Kumagai T. Satake K. Chem. Lett.  1985,  1809 
• 5f Stachel H.-D. Schorp M. Maier L. Dandl K. Liebigs Ann. Chem.  1994,  1121 
• 6 Langer P. Wuckelt J. Döring M. J. Org. Chem.  2000,  65:  729 
• Push-pull substituted heterocycles are of considerable importance. For a review, see:
• 7a Gompper R. Wagner H.-U. Angew. Chem., Int. Ed. Engl.  1988,  27:  1437 ; Angew. Chem. 1988, 100, 1492
• 7b See also: Effenberger F. Schlosser H. Bäuerle P. Maier S. Port H. Wolf HC. Angew. Chem., Int. Ed. Engl.  1988,  27:  281 ; Angew. Chem. 1988, 100, 274
• 8 Review: Langer P. Döring M. Eur. J. Org. Chem.  2002,  221 
• 11 For symmetrical derivatives, see: Langer P. Wuckelt J. Döring M. Görls H. Eur. J. Org. Chem.  2001,  1503 

9

General Procedure for the Synthesis of Unsymmetrical Oxalic Acid-bis(imidoyl) dichlorides ( 4). Oxalic acid N -phenyl- N ′-(2,4-dimethylphenyl)-bis(imidoyl) dichloride ( 4e): A toluene solution (60 mL) of 3e (2.68 g, 10.0 mmol) and of PCl₅ (4.16 g, 20.0 mmol) was refluxed for 1 h. The mixture was concentrated to 30 mL and stored at -20 °C to give a yellow precipitate. The later was isolated by filtration and recrystallized from n-heptane to give 4e as yellow crystals (2.00 g, 65%), mp 148 °C. IR (KBr): 826 (m), 1443 (w), 1521 (m), 1666 (s), 3282 (s)cm^-1. ¹H NMR (200 MHz, CDCl₃): δ = 2.23 (s, 3 H, CH₃), 2.34 (s, 3 H,CH₃), 6.94-7.66 (m, 8 H, Ar). ¹³C NMR (50 Hz, CDCl₃): δ = 17.83, 21.03, 118.65, 120.12, 120.35, 126.51, 126.73, 128.95, 129.74, 131.27, 136.47, 136.60, 142.01, 145.79. MS (EI, 70 eV):
m/z (%) = 305 (15) [M⁺], 269 (7), 166 (33), 138 (36), 77 (44), 28 (100). Anal. Calcd for C₁₆H₁₄Cl₂N₂ (305.06): C, 62.99; H, 4.58; N, 9.17. Found: C, 63.08; H, 4.96; N, 9.09. All new compounds gave satisfactory spectroscopic and analytical and/or high resolution mass data.

10

General Procedure for the Synthesis of Unsymmetrical Pyrrolo[3,2- b ]pyrrole-2,5-diones ( 6). A THF solution of LDA was prepared by addition of n-BuLi (5.15 mL, 7.92 mmol, solution in n-hexane) to a THF solution (6.1 mL) of diisopropylamine (1.22 mL, 8.71 mmol) at 0 °C. After stirring for 30 min a THF solution (33 mL) of ethyl 4-tolylacetate (1.18 mL, 6.60 mmol) was added. The solution was stirred for 1 h at 0 °C. The mixture was cooled to -78 °C and a THF solution (18 mL) of 4c (967 mg, 3.00 mmol) was slowly added. The solution was warmed to 20 °C during 14 h and was stirred for 36 h at 20 °C. The mixture was poured into an aqueous solution of ammonium chloride (300 mL, 5 M). The addition of Et₂O (200 mL) resulted in the formation of a precipitate, which was washed with Et₂O, dried in vacuo and recrystallized from DMF. For some products DMSO was used. The product 6e was obtained as an orange solid (538 mg, 35%), mp 344 °C. IR (KBr): 977 (m), 1168 (m), 1252 (m), 1301 (w), 1415 (m), 1514 (s), 1612 (m), 1653 (s), 1735 (s), 3437 (m)cm^-1. UV-Vis: 361 (4.33). ¹H NMR (200 MHz, CDCl₃): δ = 2.27 (s, 6 H, CH₃), 2.33 (s, 3 H, CH₃), 3.79 (s, 3 H, OCH₃), 6.77-7.09 (m, 16 H, Ar). ¹³C NMR (50 Hz, CDCl₃): δ = 21.12, 21.33 (CH₃), 55.57 (OCH₃), 104.72, 104.78 (C), 113.97 (CH), 125.23, 125.28 (C), 125.91 (CH), 126.83 (C), 127.42, 128.24, 128.32, 129.23, 129.69, 129.75 (CH), 131.28, 137.17, 137.18, 137.96, 137.97, 144.80, 145.06, 158.67 (C), 170.91, 171.05 (CO). MS (EI, 70 eV): m/z (%) = 512 (100) [M⁺], 497 (11), 496 (10), 236 (10), 102 (36). Anal. Calcd for C₃₄H₂₈O₃N₂ (512.6): C, 79.66; H, 5.51; N, 5.46. Found: C, 79.19; H, 5.86; N, 5.37.