Subscribe to RSS
DOI: 10.1055/s-0028-1087937
Improved Synthesis of Diquinones
Publication History
Publication Date:
24 February 2009 (online)
Abstract
Preparation of a series of substituted diquinones is reported. In most examples, inverse order of addition (addition of a dimethoxybenzene derivative to a CAN solution) has been found to produce higher yields of diquinones than the traditional protocol in which the oxidant is added to the arene.
Key words
quinones - dimerizations - oxidations - CAN - reaction protocols
- Supporting Information for this article is available online:
- Supporting Information
- 1
Posternak T. Helv. Chim. Acta 1938, 21: 1326 - 2
Smith J.Thomson RH. Tetrahedron 1960, 10: 148 - 3
Midiwo JO.Ghebremeskel Y. Bull. Chem. Soc. Ethiopia 1993, 7: 67 ; Chem. Abstr. 1994, 120, 27451 - 4
Yang X.Gulder TAM.Reichert M.Tang C.Ke C.Ye Y.Bringmann G. Tetrahedron 2007, 63: 4688 -
5a
Anderson JC.Denton RM.Wilson C. Org. Lett. 2005, 7: 123 -
5b Note: cyclization of the
corresponding diquinone to yield popolohuanone E has not yet been reported,
owing to difficulties in preparation of the requisite diquinone 1. See:
Munday RH.Denton RM.Anderson JC. J. Org. Chem. 2008, 73: 8033 -
6a
Jacob P.Callery PS.Shulgin AT.Castagnoli N. J. Org. Chem. 1976, 41: 3627 -
6b
Ali MH.Niedbalski M.Bohnert G.Bryant D. Synth. Commun. 2006, 36: 1751 - 7
Paraskevas SM.Konstantinidis D.Vassilara G. Synthesis 1988, 897 - 8
Rao DV.Ulrich H.Sayigh AAR. J. Org. Chem. 1975, 40: 2549 - 9
Posternak T.Alcalay W.Luzzati R.Tardent A. Helv. Chim. Acta 1948, 31: 525 - 10
Liebeskind LS.Riesinger SW. Tetrahedron Lett. 1991, 32: 5681 - 11
Maruyama K.Sohmiya H.Tsukube H. J. Chem. Soc., Perkin Trans. 1 1986, 2069 - 12
Buck RP.Wagoner DE. J. Electroanal. Chem. 1980, 115: 89 - 15
Hayashi N.Yoshikawa T.Ohnuma T.Higuchi H.Sako K.Uekusa H. Org. Lett. 2007, 9: 5417 - 21 Ring nitration of electron-rich
benzenes using CAN supported on silica has previously been reported.
See:
Grenier J.-L.Catteau J.-P.Cotelle P. Synth. Commun. 1999, 29: 1201 - 23 Nitration of aromatic compounds
by CAN in MeCN has been reported to be suppressed by the addition
of H2O. See:
Dinctürk S.Ridd JH. J. Chem. Soc., Perkin Trans. 2 1982, 965 - 24
Hewgill FR.Hewitt DG. J. Chem. Soc. C 1967, 723
References and Notes
Castagnoli6a reports an 85% yield of 6a and an 8% yield of 7a, while Maruyama¹¹ reports a 75% yield of 6a and does not report a yield for 7a.
14Initially this was done unintentionally.
16Applicability of the method to hydrophobic substrates becomes particularly relevant if the method is to be applied to the synthesis of popolohuanone E and related compounds, since the presumed precursor to popolohuanone E contains a large alicyclic side chain (in addition to an additional hydroxyl group; Scheme [¹] ).
17¹H NMR and ¹³C NMR spectra were obtained on crude products. These spectra indicated that compounds prepared by ‘inverse’ addition were typically devoid of any significant impurities. Products purified by recrystallization were used to obtain melting point data.
18Typical Experimental Procedure: A sample of 2,5-dimethoxytoluene (0.79 g, 5.2 mmol) was dissolved in MeCN (15 mL) and added dropwise over 20 min to a stirred solution of ceric ammonium nitrate (9.38 g, 17.1 mmol) dissolved in distilled H2O (15 mL). The mixture was stirred at r.t. for 1 h, then diluted with H2O (75 mL). The precipitate was isolated by suction filtration, rinsed with H2O, and dried under reduced pressure, yielding the product (0.57 g, 91%) as a bright yellow solid; mp 186-187 ˚C (EtOH) (lit.6a 189-190 ˚C). ¹H NMR (CDCl3): δ = 6.82 (s, 2 H), 6.71 (q, J = 1.8 Hz, 2 H), 2.11 (d, J = 1.8 Hz, 6 H). ¹³C NMR (CDCl3): δ = 186.9, 184.7, 146.2, 139.5, 135.9, 133.6, 15.6. IR: 1652, 912 cm-¹.
19
Characterization
Data (copies of spectra are provided in the Supporting Information): 6b: mp 190-192 ˚C (EtOH-CHCl3)
(lit.²4 195-197 ˚C). ¹H
NMR (CDCl3): δ = 6.76 (s,
2
H), 6.69 (s, 2 H), 1.31 (s, 18 H). ¹³C
NMR (CDCl3): δ = 186.6, 185.6, 156.3,
138.0, 137.6, 131.9, 35.3, 29.0. IR: 2957, 1658, 914 cm-¹. 6c: mp 157-159 (EtOH) ˚C. ¹H
NMR (CDCl3): δ = 6.81 (s, 2 H), 6.65
(s, 2 H), 2.45 (t, J = 7.5 Hz, 4
H), 1.50-1.60 (m, 4 H), 1.20-1.40 (m, 16 H), 0.89
(t, J = 6.9 Hz, 6 H). ¹³C
NMR (CDCl3): δ = 186.7, 185.0, 150.0, 139.2,
136.2, 132.6, 31.6, 29.2, 28.9, 28.8, 27.7, 22.6, 14.0. IR: 2917,
1661, 1644, 922 cm-¹. Anal. Calcd for
C26H34O4: C, 76.06; H, 8.35. Found:
C, 75.88; H, 8.29. 6d: mp 170-171 ˚C
(EtOH). ¹H NMR (CDCl3): δ = 6.81
(s, 2 H), 6.65 (s, 2 H), 2.50 (q, J = 7.2
Hz, 4 H), 1.17 (t, J = 7.2 Hz,
6 H). ¹³C NMR (CDCl3): δ = 186.7,
185.0, 151.1, 139.3, 136.1, 131.9, 21.9, 11.5. IR: 2955, 1662, 1646,
914 cm-¹. Anal. Calcd for C16H14O4:
C, 71.10; H, 5.22. Found: C, 71.00; H, 5.18. 6e: mp
153-154 ˚C (EtOH). ¹H NMR
(CDCl3): δ = 6.81 (s, 2 H), 6.65 (s,
2 H), 2.44 (t, J = 7.5 Hz, 4
H), 1.50-1.60 (m, 4 H), 1.00 (t, J = 7.2
Hz, 6 H). ¹³C NMR (CDCl3): δ = 186.7,
185.0, 149.7, 139.2, 136.2, 132.7, 30.8, 21.0, 13.8. IR: 1660, 1644, 917
cm-¹. Anal. Calcd for C18H18O4:
C, 72.47; H, 6.08. Found: C, 72.36; H, 6.15. 6f:
mp 167-168 ˚C (EtOH-CHCl3). ¹H
NMR (CDCl3): δ = 6.81 (s, 2 H), 6.65
(s, 2 H), 2.46 (t, J = 6.9 Hz,
4 H), 1.40-1.60 (m, 8 H), 0.95 (t, J = 6.9 Hz,
6 H). ¹³C NMR (CDCl3): δ = 186.7,
185.0, 150.0, 139.2, 136.2, 132.6, 29.7, 28.5, 22.4, 13.7. IR: 2924,
1661, 1645, 922 cm-¹. Anal. Calcd for
C20H22O4: C, 73.60; H, 6.79. Found:
C, 73.50; H, 6.79. 6g: mp 158-159 ˚C
(EtOH-CHCl3). ¹H NMR (CDCl3): δ = 6.81
(s, 2 H), 6.65 (s, 2 H), 2.45 (t, J = 6.9
Hz, 4 H), 1.50-1.60 (m, 4 H), 1.30-1.40 (m, 8
H), 0.93 (t, J = 6.9 Hz, 6 H). ¹³C
NMR (CDCl3): δ = 186.7, 185.0, 150.0,
139.2, 136.2, 132.6, 31.4, 28.8, 27.4, 22.3, 13.9. IR: 2923, 1660,
1645, 922 cm-¹. Anal. Calcd for C22H26O4:
C, 74.55; H, 7.39. Found: C, 74.47; H, 7.28. 6h: mp
190-192 ˚C (lit.9 194-195 ˚C). ¹H
NMR (CDCl3): δ = 7.12 (s, 2 H), 7.00
(s, 2 H). ¹³C NMR (DMSO-d
6): δ = 180.6, 176.8,
141.0, 137.5, 133.9, 132.0. IR: 1670, 1652, 910 cm-¹. 6i: mp 181-183 ˚C (EtOH)
(lit.9 187-188 ˚C). ¹H
NMR (CDCl3): δ = 7.41 (s, 2 H), 7.04
(s, 2 H). ¹³C NMR (CDCl3): δ = 181.7,
178.4, 139.0, 138.2, 137.7, 135.6. IR: 1667, 914 cm-¹. 6j: mp 224-225 ˚C (CHCl3). ¹H
NMR (CDCl3): δ = 7.76 (s, 2 H), 7.07
(s, 2 H). ¹³C NMR (CDCl3): δ = 181.4, 179.7,
146.4, 139.3, 134.6, 119.8. IR: 1666, 1642, 914 cm-¹. Anal.
Calcd for C12H4I2O4:
C, 30.93; H, 0.87. Found: C, 31.04; H, 0.93. 6k:
mp 189-192 ˚C (EtOH). ¹H NMR (DMSO-d
6): δ = 6.92
(s, 2 H), 6.75 (s, 2 H), 5.46 (br s, 2 H), 4.36 (s, 4 H). ¹³C
NMR (DMSO-d
6): δ = 187.2,
185.6, 150.2, 140.6, 136.4, 130.6, 57.6. IR: 3400, 1663, 923 cm-¹.
Anal. Calcd for C14H10O6: C, 61.32;
H, 3.68. Found: C, 61.26; H, 3.60. 6l:
mp 162-166 ˚C (EtOH). ¹H NMR
(CDCl3): δ = 6.89 (t, J = 1.8
Hz, 2 H), 6.81 (s, 2 H), 4.34 (d, J = 1.8
Hz, 4 H), 3.48 (s, 6 H). ¹³C NMR (CDCl3): δ = 186.1,
184.6, 145.9, 139.4, 135.9, 131.6, 67.4, 59.2. IR: 1659, 920 cm-¹.
Anal. Calcd for C16H14O6: C, 63.57;
H, 4.67. Found: C, 62.67; H, 4.52. 6m:
mp 195-196 ˚C (EtOH). ¹H NMR
(CDCl3): δ = 6.88 (s, 2 H), 6.83 (s,
2 H), 3.05 (br s, 2 H), 1.56 (s, 12 H). ¹³C
NMR (CDCl3): δ = 187.6, 185.2, 152.6,
138.1, 137.5, 131.0, 71.3, 29.0. IR: 3416, 1646, 939 cm-¹.
Anal. Calcd for C18H18O6: C, 65.45;
H, 5.49. Found: C, 65.29; H, 5.44. 6n: mp
184-186 ˚C (EtOH). ¹H NMR
(DMSO-d
6): δ = 6.95
(s, 2 H), 6.81 (s, 2 H), 4.76 (t, J = 5.4
Hz, 2 H), 3.59 (dt, J = 5.4, 6.0
Hz, 4 H), 2.55 (t, J = 6.0 Hz,
4 H). ¹³C NMR (DMSO-d
6): δ = 187.5,
185.7, 147.4, 140.5, 136.4, 134.3, 59.4, 32.6. IR: 3418, 1662, 1646,
920 cm-¹. Anal. Calcd for C16H14O6:
C, 63.57; H, 4.67. Found: C, 63.29; H, 4.56. 6o:
mp 115-117 ˚C (EtOH). ¹H NMR
(CDCl3): δ = 6.86 (s, 2 H), 6.73 (s,
2 H), 4.29 (t, J = 6.0 Hz, 4
H), 2.81 (t, J = 6.0 Hz, 4 H),
2.05 (s, 6 H). ¹³C NMR (CDCl3): δ = 186.0,
184.4, 170.7, 145.7, 139.3, 136.1, 134.1, 61.4, 28.6, 20.8. IR:
1739, 1661, 1241, 1041, 922 cm-¹. Anal.
Calcd for C20H18O8: C, 62.17; H,
4.70. Found: C, 62.17; H, 4.64. 6p: mp
116-117 ˚C (EtOH). ¹H NMR
(CDCl3): δ = 6.82 (s, 2 H), 6.77 (s,
2 H), 3.60 (t, J = 6.0 Hz, 4
H), 3.35 (s, 6 H), 2.73 (t, J = 6.0
Hz, 4 H). ¹³C NMR (CDCl3): δ = 186.5,
184.7, 146.6, 139.1, 136.2, 134.1, 69.6, 58.6, 29.1. IR: 1662, 1364,
1123, 922 cm-¹. Anal. Calcd for C18H18O6:
C, 65.45; H, 5.49. Found: C, 64.29; H, 5.42. 6q: mp
227-233 ˚C (EtOH-CHCl3). ¹H
NMR (CDCl3): δ = 8.39 (br s, 2 H),
7.67 (s, 2 H), 6.89 (s, 2 H), 1.32 (s, 18 H). ¹³C NMR
(CDCl3): δ = 185.0, 182.3, 177.8, 139.4,
138.4, 133.7, 114.8, 40.6, 27.2. IR: 3375, 1706, 1664, 1643, 1505
cm-¹. Anal. Calcd for C22H24N2O6:
C, 64.07; H, 5.87; N, 6.79. Found: C, 63.66; H, 5.85; N, 6.65. 6r: mp 234-244 ˚C (EtOH-CHCl3). ¹H
NMR (DMSO-d
6): δ = 9.87
(s, 2 H), 7.47 (s, 2 H), 6.96 (s, 2 H), 2.21 (s, 6 H). ¹³C
NMR (DMSO-d
6): δ = 185.6,
182.1, 171.4, 140.3, 140.0, 133.5, 113.9, 24.4. IR: 3317, 1682,
1634, 1520 cm-¹. Anal. Calcd for C16H12N2O6: C,
58.54; H, 3.68; N, 8.53. Found: C, 58.48; H, 3.53; N, 8.51. 6s: mp 256-260 ˚C (EtOH-DMSO). ¹H
NMR (DMSO-d
6): δ = 10.20
(s, 2 H), 7.44 (s, 2 H), 6.98 (s, 2 H), 4.52 (s, 4 H). ¹³C
NMR (DMSO-d
6): δ = 185.3,
181.7, 167.3, 140.2, 139.7, 133.7, 114.9, 43.4. IR: 3340, 1703,
1670, 1638 cm-¹. Anal. Calcd for C16H10Cl2N2O6:
C, 48.39; H, 2.54; N, 17.85. Found: C, 48.40; H, 2.51; N, 6.98.
Dimethyl acetals of 2,5-dimethoxybenzaldehyde and 2′,5′-dimethoxyacetophenone both returned only the unprotected carbonyl compounds under these reaction conditions.
22Typical reaction conditions utilized approximately 3 mL of MeCN per mmol of substrate (see typical experimental procedure). ‘Dilute’ reaction conditions utilized approximately 10 mL of MeCN-H2O (2:1) per mmol of substrate. Both employed CAN solutions that were approximately 1 M.