The Journal of Organic Chemistry
Article
3.60 (s, 3H; CH3). 13C NMR (100 MHz, CDCl3) δ 197.1, 161.4,
160.4, 138.7, 133.1, 132.7, 130.0, 128.1, 119.7, 107.5, 99.5, 55.3. UV−
vis (MeOH) λmax (ε) = 311 (6.2 × 103), 282 (6.5 × 103), 246 (1.4 ×
104), 211 (1.3 × 104) nm (cm−1 mol−1 L). IR (neat) v = 3335, 1629,
1596, 1573, 1503, 1461, 1350, 1284, 1203, 1110, 1029, 962, 920, 828,
795, 746, 711, 628, 563, 497 cm−1. HRMS (ESI/TOF) m/z: [S3 +
Na]+ calcd for C14H12O3Na, 251.0684; found, 251.0684.
General Method for the Preparation of Ketimines. All
ketimines were prepared by the high-temperature, solvent-free reaction
of amine (ethanolamine or 3,5-dimethylaniline) with the appropriate
ketone, Scheme 7. In a typical procedure, the ketone and a 10-fold
852, 816, 774, 701, 670, 561, 542, 525, 459 cm−1. HRMS (ESI/TOF)
m/z: [3c + H]+ calcd for C21H20NO2, 318.1490; found, 318.1494.
2,4-Dihydroxybenzophenone Hexylamine Schiff Base (3d).
Yellow-orange crystals (270 mg, 84% from 250 mg of 2,4-
dihydroxybenzophenone) yield from the cold methanol−water
1
solution. mp 141−147 °C. H NMR (400 MHz, CDCl3) δ 7.51 (m,
3
3H; Ar), 7.26 (m, 2H; Ar), 6.55 (d, JHH = 9.2 Hz, 1H; Ar), 6.50 (d,
3JHH = 2.6 Hz, 1H; Ar), 6.07 (dd, 3JHH = 9.2, 2.6 Hz, 1H; Ar), 3.21 (t,
3JHH = 7.0 Hz, 2H; CH2), 1.60 (q, 3JHH = 7.4 Hz, 2H; CH2), 1.34−1.16
(m, 6H; CH2), 0.83 (t, 3JHH = 7.0 Hz, 3H; CH3). 13C NMR (75 MHz,
CDCl3) δ 174.8, 173.3, 164.5, 134.0, 132.1, 129.5, 128.6, 127.7, 110.8,
106.9, 105.7, 47.2, 31.3, 30.1, 26.5, 22.4, 14.0. UV−vis (MeOH) λmax
(ε) = 337 (7.3 × 103), 305 (1.2 × 104), 211 (1.3 × 103) nm (cm−1
mol−1 L). IR (neat) v = 2954, 2927, 2856, 2550 (br), 1574, 1531,
1488, 1453, 1393, 1340, 1238, 1175, 1113, 1074, 1026, 979, 924, 851,
800, 771, 698, 634, 553 cm−1. HRMS (ESI/TOF) m/z: [3d + H]+
calcd for C19H24NO2, 298.1807; found, 298.1807.
Scheme 7. Solvent-Free Reaction of Ketone and Imine at
High Temperature Generally Yields the Ketimine in Good
Yield
2-Hydroxy-4-methoxybenzophenone Ethanolamine Schiff
Base (4). A sticky orange-brown solid was obtained in 94% (254
mg from 204 mg of 2-hydroxy-4-methoxybenzophenone) yield that is
pure by 1H NMR spectroscopy. Samples suitable for optical
characterization were obtained by passing the product through a
short column of silica gel using ethyl acetate as eluent (Rf = 0.3)
followed by the evaporation of solvent under vacuum. A fluorescent
excess of amine were combined in a small Schlenk tube, which was
purged three times with nitrogen before heating at 120 °C for 10 min
to complete the conversion. Depending on the substrate used, most or
all of the excess amine could be removed by heating the flask for 12 h
at 80 °C under high vacuum. When the product is a glaze, amine
removal is much quicker if the glaze is periodically thinned by stirring
with methanol or toluene.
1
waxy yellow solid was thus obtained in 79% overall yield. H NMR
(400 MHz, CD3OD) δ 7.58 (m, 3H; Ar), 7.35 (m, 2H; Ar), 6.58 (d,
3JHH = 9.2 Hz, 1H; Ar), 6.23 (d, 3JHH = 2.6 Hz, 1H; Ar), 6.04 (dd, 3JHH
3
= 9.2, 2.6 Hz, Ar), 3.77 (s, 3H; CH3), 3.71 (t, JHH = 5.5 Hz, 2H;
3
CH2), 3.40 (t, JHH = 5.5 Hz, 2H; CH2). 13C NMR (100 MHz,
Further purification details and characterization data are provided
below.
acetone-d6) δ 175.1, 168.3, 164.5, 134.9, 133.5, 129.9, 129.6, 128.6,
114.3, 105.8, 102.4, 62.6, 55.7, 54.0. UV−vis (MeOH) λmax (ε) = 387
(2.2 × 104), 305 (3.2 × 103) nm (cm−1 mol−1 L). IR (neat) v = 3152,
2951, 2834, 1582, 1538, 1440, 1340, 1221, 1075, 1022, 833, 799, 769,
702, 545, 493 cm−1. HRMS (ESI/TOF) m/z: [4 + H]+ calcd for
C16H18NO3, 272.1287; found, 272.1282.
4,6-Dibenzoylresorcinol Ethanolamine Schiff Base (2b). The
product was further purified by recrystallization from a mixture of
water and methanol, yielding 2b as a yellow solid in 89% (114 mg
from 101 mg of 4,6-dibenzoylresorcinol) yield. Melts with
1
decomposition. H NMR (400 MHz, CD3OD) δ 7.36 (m, 6H; Ar),
3
4-Hydroxy-2-methoxybenzophenone Ethanolamine Schiff
Base (5). The product was obtained in 93% (136 mg from 122 mg
of 4-hydroxy-2-methoxybenzophenone) yield as a red glaze. Passing
the product through a pad of silica gel using 1:9 methanol/
dichloromethane as eluent can yield a bright yellow product, Rf =
0.1, suitable for optical characterization, albeit at a lower yield of 45%.
1H NMR (300 MHz, acetone-d6) δ 7.64 (m, 2H; Ar), 7.32 (m, 3H;
7.13 (d, JHH = 7.4 Hz, 4H; Ar), 6.38 (s, 1H; Ar), 5.97 (s, 1H; Ar),
3
3
3.70 (t, JHH = 5.2 Hz, 4H; CH2), 3.41 (t, JHH = 5.2 Hz, 4H; CH2).
13C NMR (100 MHz, DMSO-d6) δ 173.7, 171.5, 139.0, 131.5, 128.9,
128.2, 127.4, 110.9, 104.9, 60.3, 51.6. UV−vis (MeOH) λmax (ε) = 393
(1.6 × 104), 317 (2.5 × 104) nm (cm−1 mol−1 L). IR (neat) ν = 2900
(br), 1556, 1435, 1301, 1250, 1143, 1080, 938, 919, 840, 782, 756, 705,
669, 591, 566, 467 cm−1. HRMS (ESI/TOF) m/z: [2b + H]+ calcd for
C24H25N2O4, 405.1814; found, 405.1812.
Ar), 6.82 (d, 3JHH = 8.1 Hz, 1H; Ar), 6.62 (d, 3JHH = 2.2 Hz, Ar), 6.56
(dd, 3JHH = 8.1 Hz, 2.2 Hz, Ar), 3.77 (t, 3JHH = 6.1 Hz, 2H; CH2), 3.40
2,4-Dihydroxybenzophenone Ethanolamine Schiff Base
(3b). All traces of leftover amine were removed by flash column
chromatography of the product using 1:9 methanol/dichloromethane.
The yellow first fraction was evaporated to give 3b in 85% (102 mg
from 100 mg of 2,4-dihydroxybenzophenone) yield. mp 186−191 °C.
1H NMR (300 MHz, CD3OD) δ 7.58 (m, 3H; Ar), 7.36 (m, 2H; Ar),
3
(t, JHH = 6.1 Hz, 2H; CH2). 13C NMR (100 MHz, acetone-d6) δ
166.9, 160.2, 158.5, 141.2, 130.01, 129.98, 128.4, 128.3, 117.5, 108.1,
99.7, 63.1, 57.1, 55.7. UV−vis (MeOH) λmax (ε) = 374 (1.6 × 104),
238 (9.3 × 103) nm (cm−1 mol−1 L). IR (neat) v = 2930 (br), 1563,
1504, 1366, 1294, 1253, 1200, 1123, 1060, 1027, 958, 836, 774, 697,
590, 548, 511, 456 cm−1. HRMS (ESI/TOF) m/z: [5 + H]+ calcd for
C16H18NO3, 272.1287; found, 272.1292. Note: Regardless of the
purification method used, solutions in acetone-d6 yield clean 1H NMR
spectra, whereas in CDCl3 and methanol-d4, there appears to be a pair
of similar compounds. We suspect this to be due to geometrical
isomerism about the CN double bond.
6.55 (d, 3JHH = 9.0 Hz, 1H; Ar), 6.14 (d, 3JHH = 2.4 Hz, 1H; Ar), 5.96
3
3
(dd, JHH3 = 9.0, 2.4 Hz, 1H; Ar), 3.71 (t, JHH = 5.4 Hz, 2H; CH2),
3.40 (t, JHH = 5.4 Hz, 2H; CH2). 13C NMR (100 MHz, CD3OD) δ
177.3, 175.9, 166.3, 135.7, 133.0, 131.0, 129.9, 129.1, 112.0, 107.6,
105.8, 61.6, 50.4. UV−vis (MeOH) λmax (ε) = 384 (8.2 × 103), 309
(1.5 × 104) nm (cm−1 mol−1 L). IR (neat) v = 1591, 1573, 1556, 1496,
1471, 1384, 1335, 1260, 1235, 1175, 1118, 1059, 980, 851, 806, 778,
717, 631, 563, 439 cm−1. HRMS (ESI/TOF) m/z: [3b + H]+ calcd for
C15H16NO3, 258.1130; found, 258.1122.
ASSOCIATED CONTENT
■
S
* Supporting Information
2,4-Dihydroxybenzophenone 3,5-Dimethylaniline Schiff
Base (3c). A yellow-orange solid was obtained in 87% (387 mg
from 300 mg of 2,4-dihydroxybenzophenone) yield from the methanol
Kinetics data, NMR spectra, expanded ab initio section, and
energy-optimized atomic coordinates for all species used in
calculations. This material is available free of charge via the
1
solution by the addition of water. mp 203−205 °C. H NMR (600
3
MHz, CDCl3) δ 7.36 (m, 3H; Ar), 7.19 (m, 2H; Ar), 6.93 (d, JHH
=
3
8.9 Hz, 1H; Ar), 6.64 (bs, 1H; Ar), 6.55 (d, JHH = 2.5 Hz, 1H; Ar),
6.39 (bs, 2H; Ar), 6.25 (dd, 3JHH = 8.9, 2.5 Hz, Ar), 2.14 (s, 6H; CH3).
13C (150 MHz, CDCl3) δ 171.9, 167.9, 161.5, 144.7, 138.2, 134.3,
133.9, 129.1, 128.9, 128.3, 126.6, 121.0, 113.4, 106.9, 104.4, 21.3. UV−
vis (MeOH) λmax (ε) = 403 (shoulder, 3.6 × 103), 332 (1.3 × 104),
287 (1.2 × 104), 240 (shoulder, 1.5 × 103) nm (cm−1 mol−1 L). IR
(neat) v = 3351, 2922, 1582, 1442, 1339, 1192, 1112, 1020, 962, 908,
AUTHOR INFORMATION
■
Corresponding Authors
F
J. Org. Chem. XXXX, XXX, XXX−XXX