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A. Raghunadh et al.
PAPER
2,2-Dibromo-1-phenylethanone (1a)
3-Hydroxypropyl (4-methylphenyl)(oxo)acetate (2j)
Pink liquid; yield: 494 mg (65%).
Br2 (29.3 g, 0.18 mol) was added dropwise over 20 min to anhyd
1,4-dioxane (60 mL) at 25–30 °C under a minimum flow of N2 and
the mixture was kept under these conditions for 30 min. A soln of
PhCOMe (10 g, 0.8 mol) in dioxane (40 mL) was added and the
mixture was stirred for another 2–3 h. The reaction was then
quenched in ice-cold H2O (1 L, 10 volumes with respect to 1,4-di-
oxane) and the solid was filtered off and washed with chilled hex-
ane; yield: 21 g (90%).
IR (neat): 669, 758, 845, 928, 1001, 1029, 1174, 1216, 1261, 1606,
1682, 1735, 2400, 2927, 2961, 3020 cm–1.
1H NMR (400 MHz, CDCl3): d = 1.25 (s, 1 H, OH), 2.02 (quint,
J = 6.4 Hz, 2 H), 2.44 (s, 3 H), 3.79 (t, J = 6 Hz, 2 H), 4.54 (t, J = 6.2
Hz, 2 H), 7.30 (d, J = 8.4 Hz, 2 H, ArH), 7.91 (d, J = 8.0 Hz, 2 H,
ArH).
13C NMR (100 MHz, CDCl3): d = 21.8, 31.3, 58.9, 63.1, 129.6,
129.8, 130.1, 146.3, 164.0, 185.8.
(Het)aryl a-Keto Esters 2a–2o, 2r, and 2s; General Procedure
The dibromo ketone (1.0 g) was dissolved in anhyd DMSO (6 mL)
under argon. (The moisture content of the DMSO should be less
than 0.5%, otherwise some keto acid will be formed in the reaction.)
The mixture was then slowly heated to 70–75 °C for 1–2 h. (Note:
If the temperature of the reaction mixture rises to above 100 °C, the
reaction will become very violent.) The mixture was kept at 70–75
°C for another 14–16 h, then cooled to r.t. The alcohol (0.6 mL) was
added and the mixture was stirred for 1–2 h. The mixture was then
diluted with H2O (60 mL) and extracted with EtOAc (4 × 30 mL).
The combined organic layer was washed successively with H2O (3
× 30 mL) and brine, dried (Na2SO4), and concentrated under re-
duced pressure. The crude products were 95–96% pure, and analyt-
ically pure samples were obtained by column chromatography
(hexane–EtOAc).
MS: m/z = 223 [M + 1], 245 [M + Na].
Ethyl (1-Tosyl-1H-indol-3-yl)(oxo)acetate (2q)
Yellow solid; yield: 527 mg (67%); mp 89–90 °C.
IR (KBr): 813, 984, 1019, 1104, 1134, 1177, 1382, 1146, 1530,
1668, 1731, 1919, 2926 cm–1.
1H NMR (400 MHz, CDCl3): d = 1.45 (t, J = 7.0 Hz, 3 H), 2.37 (s,
3 H), 4.40 (q, J = 7.2 Hz, 2 H), 7.28 (dd, J = 8.0, 4.4 Hz, 2 H, ArH),
7.39 (m, 2 H), 7.88 (d, J = 8.4 Hz, 2 H), 7.96 (dd, J = 1.6, 2.0 Hz,
1 H, ArH), 8.36 (dd, J = 2.0, 2.0 Hz, 1 H, ArH), 8.84 (s, 1 H).
13C NMR (100 MHz, CDCl3): d = 14.0, 21.5, 62.5, 113.0, 116.9,
122.8, 125.1, 126.0, 127.2, 127.5, 130.2, 134.1, 134.3, 136.7, 146.1,
161.5, 178.6.
Alkoxy(het)aryl a-Keto Esters (2p and 2q); General Procedure
The reaction was carried out as described in the general procedure
above, except that the reaction mixture was maintained at 40–45 °C
for 55–60 h after adding the DMSO at r.t.
MS: m/z = 372 [M + 1], 394 [M + 23].
Anal. Calcd for C19H17NO5S: C, 61.44; H, 4.61; N, 3.77. Found: C,
61.43; H, 4.60; N, 3.75.
Propane-1,3-diyl Bis[2-oxo-2-(het)aryl]acetates 11a, 11b, and
12; General Procedure
Methyl Oxo(phenyl)acetate (2a)
Pale-yellow liquid; yield: 445 mg (75%).
The dibromo ketone (1 g, 0.0035 mol) was dissolved in anhyd
DMSO (6 mL) under argon. (The moisture content should be less
than 0.5%, otherwise some keto acid will be formed in the reaction.)
The soln was then slowly heated to 70–75 °C and maintained at this
temperature for about 14–15 h. The mixture was then cooled to r.t.,
propane-1,3-diol (0.138 g, 0.0018 mol) was added, and the mixture
was stirred for 1–2 h. The mixture was then diluted with H2O (100
mL) and extracted with EtOAc (4 × 30 mL). The combined organic
layer was washed successively with (3 × 30 mL) and brine, dried
(Na2SO4), and concentrated under reduced pressure. The pure prod-
uct was isolated by column chromatography (hexane–EtOAc).
IR (KBr): 669, 928, 1008, 1174, 1215, 1436, 1598, 1691, 1740,
2853, 2925 cm–1.
1H NMR (400 MHz, CDCl3): d = 3.98 (s, 3 H), 7.52 (t, J = 7.8 Hz,
2 H, ArH), 7.66 (t, J = 7.4 Hz, 1 H, ArH), 8.03 (d, J = 7.6 Hz, 2 H,
ArH).
13C NMR (100 MHz, CDCl3): d = 52.7, 128.8, 130.0, 132.4, 134.9,
164.0, 186.0.
MS: m/z = 165 [M + 1], 187 [M + 23].
Prop-2-yn-1-yl Oxo(phenyl)acetate (2e)
Pale-yellow liquid; yield: 470 mg (68%).
Propane-1,3-diyl Bis[oxo(phenyl)acetate] (11a)
Pink liquid; yield: 850 mg (70%).
IR (neat): 651, 908, 1195, 1451, 1598, 1692, 1740, 2254 cm–1.
IR (neat): 761, 785, 1020, 1173, 1192, 1288, 1370, 1450, 1597,
1691, 1745, 2132, 3067, 3309 cm–1.
1H NMR (400 MHz, CDCl3): d = 2.28 (q, 2 H), 4.53 (t, J = 6.2 Hz,
4 H), 7.53 (t, J = 7.9 Hz, 4 H, ArH), 7.66 (t, J = 7.6 Hz, 2 H, ArH),
8.01 (d, J = 7.6 Hz, 4 H, ArH).
1H NMR (400 MHz, CDCl3): d = 2.60 (s, 1 H), 4.96 (s, 2 H), 7.53
(t, J = 7 Hz, 2 H, ArH), 7.68 (t, J = 7 Hz, 1 H, ArH), 8.03 (d, J = 6.8
Hz, 2 H, ArH).
13C NMR (100 MHz, CDCl3): d = 27.7, 62.3, 128.9, 129.9, 132.2,
134.9, 163.5, 185.8.
MS: m/z = 189 [M + 1], 212 [M + Na].
3-Hydroxypropyl Oxo(phenyl)acetate (2h)
Pink liquid; yield: 485 mg (65%).
MS: m/z = 341 [M + 1], 363 [M + Na].
Propane-1,3-diyl Bis[(4-methylphenyl)(oxo)acetate] (11b)
Pink liquid; yield: 860 mg (68%).
IR (neat): 786, 908, 1176, 1597, 1691, 1735, 2253, 2855, 2927,
2961, 3436 cm–1.
1H NMR (400 MHz, CDCl3): d = 0.88 (s, 1 H, OH), 2.02 (quint,
J = 6.0 Hz, 2 H), 3.78 (t, J = 7.4 Hz, 2 H), 4.54 (t, J = 6.2 Hz, 2 H),
7.51 (t, J = 7.6 Hz, 2 H, ArH), 7.66 (t, J = 7.4 Hz, 1 H, ArH), 8.00
(d, J = 7.2 Hz, 2 H, ArH).
13C NMR (100 MHz, CDCl3): d = 31.3, 58.9, 63.2, 128.8, 129.9,
132.3, 134.9, 163.8, 186.1.
IR (neat): 756, 1022, 1172, 1216, 1305, 1606, 1682, 1737, 2927,
3021 cm–1.
1H NMR (400 MHz, CDCl3): d = 2.27 (t, J = 6.2 Hz, 2 H), 2.44 (s,
6 H), 4.51 (t, J = 6.2 Hz, 4 H), 7.31 (d, J = 8 Hz, 4 H, ArH), 7.90 (d,
J = 8 Hz, 4 H, ArH).
13C NMR (100 MHz, CDCl3): d = 21.9, 27.7, 62.2, 129.6, 129.8,
130.1, 146.3, 163.7, 185.5.
MS: m/z = 209 [M + 1], 231 [M + Na].
MS: m/z = 369 [M + 1], 391 [M + Na].
Synthesis 2012, 44, 283–289
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