Schiff Base Metal-Catalyzed 1,3-Dipolar Cycloadditions
J. Chin. Chem. Soc., Vol. 56, No. 5, 2009 1015
while the benzyl ester hydrochloride crystallized. The prod-
uct was collected after filtration and recrystallized from an
absolute ethanol-ether mixture. Yields of benzyl ester hy-
drochlorides of L-phenylglycine, L-phenylalanine: >95%.
Yields of benzyl ester hydrochlorides of L-valine, L-iso-
leucine: approx. 70%. Yields of benzyl ester hydrochlor-
ides L-leucine, L-methionine, and L-glutamic acid: approx.
85%.
1H, -CH=N), 12.71 (S, 1H, -OH). 13C NMR: d 40.02,
67.11, 73.10, 117.15, 118.46, 118.72, 126.91, 128.25,
128.42, 128.57, 128.64, 129.62, 131.80, 132.86, 135.43,
136.64, 161.03, 167.01, 170.65. MS: m/z = 360.4, 382.0,
336.2, 397.9 (MS+). Anal. Calcd. for C23H21O3N: C 76.86,
H 5.89, N 3.89; Found: C 76.68, H 6.00, N 3.61.
SalValOCH2Ph (5c)
Yield: 91%. Mp: 53.4-54.5 °C. IR (KBr): 3448, 1731,
1629, 1279, 1152 cm-1. 1H NMR: d 0.97 (d, J = 6.7 HZ, 6H,
CH3), 2.41 (m, J = 6.7 HZ, J = 6.1 HZ, 1H, CH), 3,79 (d, J =
6.1 HZ, 1H, N-CH), 5.22 (s, 2H, -OCH2), 6.88~7.38 (m,
Preparation of the free amino acid benzyl esters
To a suspension of 20 mmol of the amino acid benzyl
ester hydrochlorides in 50 mL of chloroform, 4 g (40
mmol) of triethylamine was added over a period of ten min-
utes at 0-5 °C. Subsequently, 100 mL of absolute ether was
added and then the mixture was allowed to stand for ten
minutes. Afterwards the precipitated triethylammonium
hydrochloride was filtered off and the ethereal solution was
concentrated in vacuo with rigid exclusion of moisture.
The remaining pale yellow oil was the amino acid benzyl
ester. Yield: >90%.
10H, Ar-H), 8.33 (s, 1H, -CH=N), 13.15 (s, 1H, -OH). 13
C
NMR: d 18.19, 19.43, 31.92, 66.82, 77.91, 117.22, 118.58,
118.73, 128.26, 128.37, 128.63, 131.79, 132.86, 135.62,
161.23, 166.72, 170.90. MS: m/z = 312.4, 334.1, 350.1
(MS+). Anal. Calcd. for C19H21O3N: C 73.29, H 6.80, N
4.50; Found: C 73.51, H 6.91, N 4.58.
SalLeuOCH2Ph (5d)
Yield: 93%. Mp: 63-64.5 °C. IR (KBr): 3465, 1740,
1631, 1278, 1142 cm-1. 1H NMR: d 0.84 (m, 6H, CH3), 1.53
(m, 1H, -CH), 1.79 (m, 2H, -CH2), 4.04 (m, 1H, -CH), 5.11
(s, 2H, -OCH2), 6.79~7.29 (m, 9H, Ar-H), 8.29 (s, 1H,
-CH=N), 12.96 (s, 1H, -OH). 13C-NMR: d 21.55, 23.06,
24.52, 42.34, 66.92, 69.79, 117.20, 118.62, 118.76, 128.17,
128.64, 131.77, 132.83, 135.61, 161.12, 166.52, 171.46.
MS: m/z = 326.2, 348.1, 363.9 (MS+). Anal. Calcd. for
C20H23O3N: C 73.82, H 7.10, N 4.30; Found. C 73.88, H
6.95, N 4.38.
General procedure for the preparation of amino acid
benzyl ester Schiff bases (5a-g and 8a-b)
All Schiff bases were prepared in a way described be-
low: 10 mmol free amino acid benzyl esters was dissolved
in 10 mL methanol, and 10 mmol salicylaldehyde or 2-hy-
droxy-1-naphthaldehyde was added therein rapidly. Imme-
diately, the color of the solution changed from colorless to
bright lemon-yellow with a small quantity of heat released.
The reaction was allowed to come to completion by stirring
for not less than 5 minutes at room temperature and then the
products precipitated directly from methanol. The obtained
yellow solid was further purified by recrystallization from
methanol.
SalILeuOCH2Ph (5e)
Yield: 82%. Mp: 36-37 °C. IR (KBr): 3436, 1746,
1630, 1281 cm-1. 1H NMR: d 0.92 (m, 6H, CH3), 3.88 (d,
1H, -CH), 5.22 (s, 2H, -OCH2), 6.91~7.39 (m, 9H, Ar-H),
8.34 (s, 1H, -CH=N), 13.14 (s, 1H, -OH). 13C NMR: d
11.27, 15.88, 25.04, 38.41, 66.82, 77.23, 117.23, 118.50,
118.74, 128.26, 128.36, 128.61, 131.80, 132.94, 135.58,
161.26, 166.67, 170.88. MS: m/z = 326.0, 348.4, 363.9
(MS+). Anal. Calcd. for C20H23O3N: C 73.82, H 7.10, N
4.30; Found. C 73.44, H 7.13, N 4.27.
SalPhgOCH2Ph (5a)
Yield: 96%. Mp: 90-91.3 °C. IR (KBr): 3449, 1732,
1
1625, 1280, 1257, 1150 cm-1. H NMR: d 5.21 (m, 3H,
-OCH2, -CH), 6.87~7.46 (m, 14H, Ar-H), 8.37 (s, 1H,
-CH=N), 13.12 (s, 1H, -OH). 13C NMR: d 67.23, 74.85,
117.26, 118.67, 118.83, 127.78, 128.01, 128.33, 131.96,
133.06, 135.45, 137.02, 161.12, 166.99, 170.10. MS: m/z =
346.2, 368.0, 383.9 (MS+). Anal. Calcd. for C22H19O3N: C
75.53, H 5.56, N 4.06. Found: C 75.38, H 5.76, N 3.90.
SalPheOCH2Ph (5b)
SalMetOCH2Ph (5f)
Yield: 90%. Mp: 58.4-59.7 °C. IR (KBr): 3437, 1735,
1727, 1632, 1296, 1282, 1160, 1150 cm-1. 1H NMR: d 2.22
(m, 2H, -CH2), 2.35 (m, 1H, -CH2), 2.50 (m, 1H, -CH2),
3.68 (s, 2H, -SCH2), 4.21 (m, 1H, -CH), 5.19 (s, 2H,
-OCH2), 6.89~7.39 (m, 14H, Ar-H), 8.33 (s, 1H -CH=N),
12.85 (s, 1H, -OH). 13C MNR: d 27.25, 32.26, 36.02, 67.09,
69.58, 117.20, 118.45, 118.83, 127.08, 128.18, 128.43,
128.54, 128.66, 128.82, 132.02, 133.08, 135.46, 138.06,
Yield: 97%. Mp: 90.7-91.5 °C. IR (KBr): 3440, 1736,
1636, 1281, 1261, 1151 cm-1. 1H NMR: d 3.14 (dd, J = 8.75
HZ, J = 13.6 HZ, 1H, -CH2), 3.37 (dd, J = 13.6 HZ, J = 5.0
HZ, 1H, -CH2), 4.21 (dd, J = 5.0 HZ, J = 8.75 HZ, 1H, -CH),
5.19 (s, 2H, -OCH2), 6,83~7.34 (m, 14H, Ar-H), 7.98 (s,