JOURNAL OF CHEMICAL RESEARCH 2008 313
(5-Methoxymethyl-2-methylfuran-3-yl)phenylmethanone (4g): 1H
NMR (400 MHz, CDCl3) δ7.79 (2H, d, J = 7.2 Hz), 7.57 (1H, t,
J = 7.2 Hz), 7.48 (2H, t, J = 7.2 Hz), 6.52 (1H, s), 4.37 (2H, s), 3.40
(3H, s), 2.54 (3H, s); 13C NMR (100 MHz, CDCl3) δ191.2, 160.0,
149.3, 139.1, 132.2, 128.9, 128.9, 128.4, 128.4, 121.1, 111.3, 66.1,
58.1, 14.3; MS: m/z 230 (M+, 8%); IR (neat) 3028, 2974, 2926, 1673,
1601, 1557, 1453, 1370, 1234, 733 cm-1; Anal. calcd for C14H14O3:
C, 73.03; H, 6.13. Found: C, 73.0; H, 6.2.
Table 1 Preparation of substituted furans
R1
R1
R2
R1
R2
R2
(NH4)2S2O8
PhSeBr
THF, r.t.
O
O
O
O
O
3
O
O
C
OH, 60
DMF, R
OR3
SePh
1
3
4
(5-Ethoxymethyl-2-methylfuran-3-yl)phenylmethanone (4h): 1H
NMR (400 MHz, CDCl3) δ7.80 (2H, d, J = 7.2 Hz), 7.59 (1H, t,
J = 7.2 Hz), 7.49 (2H, t, J = 7.2 Hz), 6.53 (1H, s), 4.36 (2H, s), 3.49
(2H, q, J = 6.8 Hz), 2.52 (3H, s), 1.13 (3H, t, J = 6.8 Hz); 13C NMR
(100 MHz, CDCl3) δ193.2, 160.8, 149.5, 139.2, 132.8, 129.1, 129.1,
128.5, 128.5, 122.0, 111.5, 66.5, 64.2, 15.0, 14.4; MS: m/z 244 (M+,
12%); IR (neat) 3026, 2974, 2924, 1674, 1600, 1557, 1455, 1235,
734 cm-1;Anal. calcd for C15H16O3: C, 73.75; H, 6.60. Found: C, 73.8;
H, 6.5.
Entry R1
R2
R3
Products/
yieldsa/%
1
2
3
4
5
6
7
8
CH3
CH3
CH3
CH3
OCH3
OCH3
OC2H5
OC2H5
CH3
4a/80
4b/76
4c/82
4d/76
4e/84
4f/83
4g/70
4h/68
C2H5
CH3
C2H5
CH3
CH3
CH3
C2H5
–CH2CH2CH2–
–CH2C(CH3)2CH2–
Ph
Ph
We thank the Natural Science Foundation of Yunnan
University (No. 2007Q007A) for financial support.
CH3
CH3
aAll products were identified by 1H NMR, IR, MS and elemental
analysis. bIsolated yield.
Received 1 February 2008; accepted 21 April 2008
on thin film or in KBr. Elemental analyses were performed on a Flash
EA1112 instrument. DMF was dried with calcium hydride. THF
was distilled from sodium/benzophenone immediately prior to use.
Compounds 3 were prepared as previously described.32
References
1
F.M. Dean, Advances in heterocyclic chemistry, ed. A.R. Katritzky,
Academic Press, New York, 1982, Vol. 30, pp. 167–283.
F.M. Dean and M.V. Sargent, Comprehensive heterocyclic chemistry, eds
C.W. Bird and G.W.H. Cheeseman, Pergamon Press, New York, 1984,
Typical procedure for the preparation of 5-methoxymethyl-2-
methylfuran-3-carboxylic acid methyl ester (4a): To a solution of
selenocyclic enol ether 3a (1 mmol) in dry DMF (5 ml) was added
ammonium persulfate (2 mmol) and methanol (1 ml). The mixture
was stired at 60°C for 3 h. Ethyl acetate (5 ml) and water (5 ml) were
added and the water layer was separated and extracted with ethyl
acetate (5 ml × 3). The organic layers were combined, washed with
brine and water and dried over MgSO4. After evaporation of solvent,
the oily residue was subjected to preparative TLC on silica gel with
ethyl acetate and light petroleum (1:9) as eluent to give 148 mg of
2
3
4
5
6
7
F. Vernin, ed. The chemistry of heterocyclic flavoring and aroma
compounds, Ellis Horwood Press, Chichester, 1982.
8
I. Kubo, Y.W. Lee, V. Balogh-Nair, K. Nakanishi and A. Chapya, J. Chem.
Soc., Chem. Commun., 1976, 949.
1
4a (80% isolated yield). yellow oil; H NMR (400 MHz, CDCl3)
9
A.I. Meyers, Heterocycles in organic synthesis, Wiley-Interscience Press,
New York, 1974.
δ6.57 (1H, s), 4.33 (2H, s), 3.82 (3H, s), 3.36 (3H, s), 2.58 (3H, s);
13C NMR (100 MHz, CDCl3) δ164.3, 159.7, 149.3, 113.8, 110.2,
66.0, 57.8, 51.3, 13.8; MS: m/z 184 (M+, 8%), 43 (100); IR (neat)
2951, 1719, 1617, 1581, 1443, 1231, 1083, 778 cm-1; Anal. calcd for
C9H12O4: C, 58.69; H, 6.57. Found: C, 58.6; H, 6.5.
10 B.H. Lipshutz, Chem. Rev., 1986, 86, 795.
13 T.L. Gilchrist, J. Chem. Soc., Perkin Trans. 1, 1999, 2849.
17 T.H. Brown, M.A. Armitage, R.C. Blakemore, P. Blurton, G.J. Durant,
19 Y. Kobayashi, M. Nakao, G. Biju Kumar and K. Kishihara, J. Org. Chem.,
5-Ethoxymethyl-2-methylfuran-3-carboxylic acid methyl ester (4b):
1H NMR (400 MHz, CDCl3) δ6.58 (1H, s), 4.39 (2H, q, J = 7.0 Hz),
3.82 (3H, s), 3.49 (2H, s), 2.60 (3H, s), 1.13 (3H, t, J = 7.0 Hz); 13
C
NMR (100 MHz, CDCl3) δ165.9, 160.6, 155.9, 111.0, 106.3, 67.0,
64.1, 51.7, 14.9, 14.0; MS: m/z 198 (M+, 12%), 43 (100); IR (neat)
2985, 2823, 1716, 1608, 1581, 1410, 1377, 1232, 1210, 779 cm-1;
Anal. calcd for C10H14O4: C, 60.59; H, 7.12. Found: 60.7; H, 7.0.
5-Methoxymethyl-2-methylfuran-3-carboxylic acid ethyl ester (4c):
1H NMR (400 MHz, CDCl3) δ6.58 (1H, s), 4.33 (2H, s), 4.28 (2H, q,
J = 7.1 Hz), 3.36 (3H, s), 2.57 (3H, s), 1.34 (3H, t, J = 7.1 Hz); 13C
NMR (100 MHz, CDCl3) δ163.9, 159.5, 149.3, 114.0, 110.3, 67.0, 60.1,
57.7, 14.3, 13.8; MS: m/z 198 (M+, 29%), 43 (100); IR (neat) 2984,
2931, 2823, 1715, 1607, 1581, 1411, 1377, 1230, 1208, 1080, 779 cm-1;
Anal. calcd for C10H14O4: C, 60.59; H, 7.12. Found: 60.5; H, 7.2.
5-Ethoxymethyl-2-methylfuran-3-carboxylic acid ethyl ester (4d): 1H
NMR (400 MHz, CDCl3) δ6.58 (1H, s), 4.39 (2H, s), 4.30–4.25 (4H,
m), 2.58 (3H, s), 1.35 (3H, t, J = 6.8 Hz), 1.14 (3H, t, J = 7.0 Hz); 13
C
NMR (100 MHz, CDCl3) δ166.1, 160.6, 155.8, 111.7, 105.7, 67.1, 64.3,
60.4, 14.9, 14.1, 13.9; MS: m/z 212 (M+, 16%), 43 (100); IR (neat) 3060,
2931, 2866, 1717, 1601, 1578, 1493, 1453, 1370, 1069, 759, 697 cm-1;
Anal. calcd for C11H16O4: C, 62.25; H, 7.60. Found: C, 62.2; H, 7.7.
2-Methoxymethyl-6,7-dihydro-5H-benzofuran-4-one (4e): 1H NMR
(400 MHz, CDCl3) δ6.59 (1H, s), 4.38 (2H, s), 3.38 (3H, s), 2.89 (2H,
t, J = 6.3 Hz), 2.49 (2H, t, J = 6.1 Hz), 2.20–2.14 (2H, m); 13C NMR
(100 MHz, CDCl3) δ194.4, 167.6, 151.8, 121.7, 105.9, 66.1, 58.0,
37.6, 23.4, 22.5; MS: m/z 180 (M+, 25%), 149 (100); IR (neat) 2924,
1638, 1219, 757 cm-1; Anal. calcd for C10H12O3: C, 66.65; H, 6.71.
Found: C, 66.7; H, 6.8.
35 M. Tiecco, L. Testaferri, M. Tingoli and F. Marini, Synlett., 1994, 373.
2-Methoxymethyl-6,6-dimethyl-6,7-dihydro-5H-benzofuran-4-
1
one (4f): H NMR (400 MHz, CDCl3) δ6.58 (1H, s), 4.38 (2H, s),
3.38 (3H, s), 2.75 (2H, s), 2.37 (2H, s), 1.14 (6H, s); 13C NMR (100
MHz, CDCl3) δ195.4, 166.2, 153.4, 122.5, 106.8, 65.9, 58.9, 50.9,
38.8, 34.4, 29.4, 27.5; MS: m/z 208 (M+, 48%), 177 (96), 152 (100);
IR (neat) 2922, 1637, 1217, 757 cm-1; Anal. calcd for C12H16O3: C,
69.21; H, 7.74. Found: C, 69.3; H, 7.8.