SOLVENT-FREE SYNTHESIS OF SCHIFF-BASE LIGANDS
375
1
3
C (100 MHz) NMR spectra were recorded on a Bruker DPX-400 high
TABLE 1. Optimization of the reaction between 1 and 2a
under microwave irradiation (800 W)
performance digital FT NMR spectrometer, with tetramethylsilane as
the internal standard for solutions in deuteriochloroform. J values are
given in hertz. Optical rotations were recorded using an Perkin-Elmer
Model 341 polarimeter. HPLC measurements were performed with BIO-
RAD instrument. Separation were carried out on Chiralcel OD column
a
Entry
Amine
Equ.
Temp. (8C)
Time (min)
Yield (%)
1
2
3
2a
2a
2a
1.1
1.1
1.1
110
120
150
4
4
4
91
96
100
(
250 3 4.60 mm) with hexane/2-propanol (85:15) as eluent. TLC plates
were purchased from Fluka.
a
1
Yields determined by H NMR.
General Classical Procedure for the Preparation of the
Chiral Schiff-Base Ligands (3a-f) Based on Ferrocene
1
23,98, 124.01, 125.40, 125.70, 127.39, 128.91, 130.87, 134.05, 159.87.
Chiral amines (2a-f) were added to a solution of ferrocene carbalde-
hyde 1 in 10 mL of ethanol. The reaction was then heated at reflux to 8
h. The ethanol was removed and the residue was washed three times
with ether and then crystallized from mixture of chloroform and hexane
to give a solid.
Anal. Calcd. for C23
H,3.85; N,5.70.
H21NFe: C,75.24; H,3.81; N,5.73. Found: C,75.89;
0
(
1S, 2S)-N,N -Cyclohexane-1,2-bis((ferrocenylmethylene)amine
20
1
3
f. (0.450g, %75), mp: 1378C, [a]D 5 1458 (C51, CHCl
3
); H NMR
(
1
400 MHz, CDCl
0H), 4.38 (s, 4H), 4.68 (d, 4H J 5 7 Hz), 8.22 (s, 2H);
3
) d 1.46 (m, 4H), 1.73 (m, 4H), 3.27 (m, 2H), 4.19 (s,
General Microwave Irradiation Procedure for the
Preparation of the Chiral Schiff-Base Ligands (3a-f) Based
on Ferrocene
13C
NMR (100
MHz, CDCl
Calcd. for C28
3
), d 24.59, 33.50, 68.26, 69.09, 69.93, 73.20, 160.52. Anal.
Fe : C,66.27; H,5.92; N,4.73. Found: C,66.89; H,5.95;
H
30
N
2
2
General reaction protocol for the synthesis of imines: a mixture of fer-
rocene carbaldehyde 1 and the chiral amines (2a-f) was homogenized
and subjected to microwave irradiation. At the end of irradiation, the
reaction mixture was cooled to room temperature. The residue was
washed with ether and then crystallized from mixture of chloroform and
hexane to give the pure imine as a solid.
N,4.75.
General procedure for the asymmetric Henry reaction. Asymmetric
Henry Reaction was performed according to our previous method proce-
dure published in literature.
27,29
RESULTS AND DISCUSSION
(
1S, 2R)-2-(ferrocenylideneamino)-1,2-diphenylethan-1-ol
1
a. (0,315 g, 77%), mp: 179-180 8C; [a]2 5 1102.58 (c 2, CH
0
3
2 2
Cl ); H
2a was used to achieve optimization reaction conditions
for preparation of chiral Schiff-bases. Thus, ferrocene carbal-
dehyde 1 and 2a were mixed and irradiated by the START
lab station. Reaction time and reaction temperature were
decided based on previous literature studies. Hence, opti-
mum reaction conditions were selected as a temperature of
D
NMR (400 MHz, CDCl
.45 (d, 1H J 5 6.4 Hz), 4.59-4.61 (d, 2H J 5 6.8 Hz), 5.10-5.12 (d, 1H, J 5
.8 Hz), 7.27-7.37 (m, 10H), 8.06 (s, 1H) C NMR (100 MHz, CDCl ), d
3
7.49, 67.92, 68.81, 69.02, 69.82, 70.53, 70.85, 73.18, 76.05, 79.96,126.45,
27.21, 127.34, 128.55, 128.65, 141.21, 1063; IR: m 3140, 2954, 2864, 1645,
496, 1452, 1375, 1259, 1060, 1041, 925, 822, 758, 713, 508, 483 Anal. Calcd
3
) d 2.64 (br s, 1H), 3.98 (s, 5H), 4.35 (s, 2H), 4.44-
4
4
6
1
1
13
1
1
508C and a reaction time of 4 min (entry 3, Table 1). The
high yields were obtained under these optimized conditions
for C25
H23FeNO: C,73.36; H,5.66; N,3.42. Found: C,73.33; H,5.69; N,3,41.
(
2S)-2-(ferrocenylideneamino)-2-phenylethan-1-ol 3b. (0.27 g,
for all the reactions.
20
1
8
0%), mp: 161–162 8C, [a]D 5 134.58 (c 2,CH
CDCl
.48-7.28 (m, 5H), 8.27 (s 1H); C NMR (100 MHz,CDCl ), d 69.13,
3
0.58, 71.04, 76.91, 78.81, 79.40, 116.40, 122.17, 127.51, 128.20, 161.84,
66.28; IR: m 3249, 3089, 3056, 3024, 2921, 2915, 2858, 1638, 1496, 1458,
394, 1391, 1342, 1252, 1201, 1092, 1027, 996, 829, 752, 701, 597, 539,
08, 496; Anal. Calcd for C19H19FeNO: C,68.49; H,5.75; N,4.20. Found:
C,68.43; H,5.80; N,4.25.
2
Cl
2
); H NMR (400 MHz,
Results show that microwave heating offers advantages
over conventional heating such as shorter reaction times and
improved yields (Table 2).
The ferrocene carbaldehyde was easily reacted with differ-
ent chiral amino alcohols and amines in ethanol to provide
chiral Schiff-bases 3a-f based on ferrocene with high yield as
shown in Scheme 1.
The catalytic activities of the chiral Schiff-bases 3a-c were
studied for the addition of nitro-methane to p-nitrobenzalde-
hyde. According to conditions previously reported
reaction was initially carried out at room temperature using 10
mol % of catalyst and copper triflate as the source of metal ion
for 40 h (Table 3). The experimental results show that using
organic base (triethylamine) increases the reaction yield, but
resulted in reduction of enantioselectivity as shown in Table 4.
3
) d 3.03 (br s, 1H), 4.10 (m, 7H), 4.38-4,39 (m, 4H), 4.85 (s, 1H),
13
7
7
1
1
5
(
2R)-2-(ferrocenylideneamino)-1,1,3-triphenyl-propan–1-ol
c. (0.390 g, 78%), mp: 197-198 8C, [a]2 5 1117.18 (c 2, CH
0
D
1
27,29
3
2
Cl
) d 2.81 (br s, 1H), 3.74 (s, 5H), 4.16-4.44 (m,
H), 4.53-4.51 (d,1H J 5 8 Hz), 4.59-4.61 (d, 1H J 5 8 Hz), 7.00-7.64 (m,
2
); H
the
NMR (400 MHz, CDCl
3
4
1
6
1
3
13
3
5H), 7.74 (s, 1H); C NMR (100 MHz, CDCl ), d 36.86, 53.45, 66.57,
8.87, 69.62, 69.93, 70.31, 77.72, 79.18, 125.53, 125.92,125.99, 126.44,
26.56,127.84, 128.09, 128.23, 128.39,144.72, 1601.90; IR: m 3472, 3095,
062, 3029,2956, 2883, 2930, 1635, 1503, 1456, 961, 716. Anal. Calcd. for
C
32
H29NOFe: C,77.00; H,5.85; N,2.80. Found: C,76.89; H,5.95; N,2.75.
TABLE 2. Synthesis of chiral Schiff-bases 3a-f under optimum
microwave heating and classical conditions
(
1R)-2-(ferrocenylideneamino)-2-ethyl-cyclohexane 3d. (0,605g,
2
0
1
8
1%), mp: 76-778C, [a] 5 2458 (C51, CHCl
3
); H NMR (400 MHz,
D
CDCl
3
) d 0.99-1.46 (m, 10H), 1.78 (m, 4H), 2.87 (m, 1H) 4.19(s, 5H), 4.36
a
b
Entry
Amines
Microwave (Yield , %)
Thermal (Yield , %)
13
(
s, 2H), 4.70-4.62 (d, J 5 31,6 Hz), 8.06 (s, 1H), C NMR (100 MHz,
CDCl
3
), d 20.16, 26.20, 26.63, 29.40, 30.40, 43.47, 68.84, 70.08, 72.38,
25NFe: C, 70.60; H,7.79; N,4.33.
1
2
3
4
5
6
2a
2b
2c
2d
2e
2f
100
93
99
95
93
77
80
78
81
76
75
81.18, 158.22. Anal. Calcd. for C19
H
Found: C,70.69; H,7.95; N,4.25.
(1S)-2-(ferrocenylideneamino)-2-ethyl-napthlane 3e. (0,650g, 76%),
2
0
1
mp: 137-1388C, [a] 5 264,58 (C51, CHCl
3
); H NMR (400 MHz,
) d 1.75-1.77 (d, 3H J 5 6.8 Hz), 4.04 (s, 5H), 4.37 (s, 2H) , 4.66 (s,
H), 4.72 (s, 1H), 5.29 (q, 1H, J 6.4 Hz), 7.49-8.24 (m, 7H), 8.26 (s, 1H).
D
100
CDCl
3
a
1
1
Yields determined by H NMR.
13
b
C NMR (100 MHz, CDCl
3
), d 23.77, 68.31, 68.78, 69.93, 68.93, 70.39,
Yields determined after purification.
Chirality DOI 10.1002/chir