8
2
S. Lal, T.J. Snape / Journal of Molecular Catalysis B: Enzymatic 83 (2012) 80–86
per 2.0 mmol of amine). The resulting suspension was stirred
at room temperature for 4 h. After which, it was filtered and
evaporated. The crude N-acylated product was purified by flash
NMR (CDCl , 300 MHz): ı 2.16 (s, 3H), 2.30 (s, 3H), 7.10 (d, 2H,
3
13
J = 9.0 Hz), 7.37 (d, 2H, J = 9.0 Hz); C NMR (CDCl , 75 MHz): ı 20.9,
3
+
24.55, 120.2, 129.5, 134.0, 135.5, 168.7; MS (ESI , m/z): 149 (50%),
−
1
chromatography (SiO ) to yield the pure amide.
106 (98), 107 (100); IR (neat): ꢀmax/cm 1660 (C O stretching),
2
1
548 (NH bending), 3289 (NH stretching).
4 -tert-Butylacetanilide (Sigma–Aldrich): brown crystals (41%
ꢀ
2.2.6. General procedure for the acetone oxime enhanced
1
synthesis of amides with catalytic acetone oxime
yield, eluted at 35% EtOAc/Petrol); R (50% EtOAc/Petrol): 0.28;
H
f
To a solution of vinyl acetate (2 equiv.) in MTBE (15 mL) was
added the amine (1 equiv., 0.13 M), CAL-B (1.5 g per 2.0 mmol of
amine), acetone oxime (0.1 equiv.) and 4 A˚ molecular sieves (1.0 g
per 2.0 mmol of amine). The resulting solution was stirred at room
temperature for 4 h. After which, it was filtered and evaporated.
The crude reaction product was purified by flash chromatography
NMR (CDCl , 300 MHz): ı 1.30 (s, 9H), 2.17 (s, 3H), 7.32–7.42 (m,
3
4H); 13C NMR (CDCl , 75 MHz): ı 24.5, 31.4, 34.3, 120.0, 125.8,
3
+
135.4, 147.3, 169.0; MS (ESI , m/z): 191 (26%), 176 (66), 134 (100);
−
1
IR (neat): ꢀmax/cm
1515 (C O stretching), 1664 (NH bending),
3251 (aromatic C H), 1375 (tert-butyl).
ꢀ
4 -Butoxyacetanilide (Sigma–Aldrich): white crystals (41%
1
(
SiO ) to yield the pure amide.
yield, eluted at 30% EtOAc/Petrol); R (50% EtOAc/Petrol): 0.20;
H
2
f
NMR (CDCl , 300 MHz): ı 0.96 (t, 3H, J = 7.5 Hz), 1.44–1.54 (m, 2H),
3
2
.3. Characterisation data
1.70–1.79 (m, 2H), 2.15 (s, 3H), 3.93 (t, 2H, J = 6.0 Hz), 6.84 (d, 2H,
J = 9.0 Hz), 7.08 (s, 1H), 7.36 (d, 2H, J = 9.0 Hz); 13C NMR (CDCl3,
75 MHz): ı 13.9, 19.3, 24.2, 31.4, 68.0, 114.7, 122.1, 131.0, 156.1,
N-benzylacetamide (Sigma–Aldrich): off white crystals (62%
1
+
yield); R (50% EtOAc/Petrol): 0.21; H NMR (CDCl , 300 MHz): ı
2
168.7; MS (ESI , m/z): 207 (24%), 151 (16), 109 (100); IR (neat):
f
3
13
−1
.03 (s, 3H), 4.43 (d, 2H, J = 6.0 Hz), 7.28–7.34 (m, 5H); C NMR
ꢀmax/cm 1541 (C O stretching), 1658 (NH bending), 3305 (aro-
(
1
ꢀ
(
CDCl , 75 MHz): ı 23.07, 43.57, 127.38, 127.74, 128.61, 138.34,
matic C H), 1368 (alkyl chain).
3
+
70.35; MS (ESI , m/z): 149 (82%), 106 (99), 91 (30); IR (neat):
N-(2,3-dihydro-1H-inden-5-yl)acetamide (Acros): light yel-
−1
max/cm 1546 (C O stretching), 1646 (NH bending), 2926, 3289
low crystals (65% yield, eluted at 30% EtOAc/Petrol); Rf (50%
1
aromatic C H).
EtOAc/Petrol): 0.32; H NMR (CDCl , 300 MHz): ı 2.01–2.11 (m, 2H),
3
13
Acetanilide (Sigma–Aldrich): white crystals (84% yield, eluted
2.16 (s, 3H), 2.83–2.91 (q, 4H, J = 9.0 Hz), 7.14 (s, 2H), 7.44 (s, 1H);
C
1
at 50% EtOAc/Petrol); R (50% EtOAc/Petrol): 0.27; H NMR (CDCl3,
NMR (CDCl , 75 MHz): ı 23.9, 25.7, 32.2, 32.8, 116.8, 118.5, 124.1,
f
3
+
3
7
1
00 MHz): ı 2.18 (s, 3H), 7.10 (t, 1H, J = 7.5 Hz), 7.32 (t, 2H, J = 7.5 Hz),
136.3, 139.9, 144.8, 169.3; MS (ESI , m/z): 175 (46%), 132 (100),
1
3
−1
.50 (d, 2H, J = 6.0 Hz); C NMR (CDCl , 75 MHz): ı 24.5, 120.2,
133 (84); IR (neat): ꢀmax/cm 1538 (C O stretching), 1656 (NH
3
+
24.3, 129.0, 138.1, 169.2. MS (ESI , m/z): 135 (30%), 136 (3), 93
bending), 3276 (aromatic C H).
−
1
(
100); IR (neat): ꢀmax/cm 1541 (C O stretching), 1698 (NH bend-
2-Acetamido-5,6,7,8-tetrahydronaphthalene
ing), 3136, 3546 (aromatic C H), 3614 (NH stretching).
(Sigma–Aldrich): light brown crystals (54% yield, eluted at
ꢀ
1
4
-Hydroxyacetanilide (Sigma–Aldrich): off white crystals
25% EtOAc/Petrol); R (50% EtOAc/Petrol): 0.31; H NMR (CDCl3,
f
(
48% yield, eluted at 60% EtOAc/Petrol); R (50% EtOAc/Petrol): 0.20;
300 MHz): ı 1.79 (s, 4H), 2.16 (s, 3H), 2.73 (s, 4H), 7.00 (d, 1H,
J = 9.0 Hz), 7.19 (d, 1H, J = 9.0 Hz), 7.29 (s, 1H, J = 7.3); C NMR
f
1
13
H NMR (DMSO, 300 MHz): ı 2.01 (s, 3H), 6.70 (d, 2H, J = 9.0 Hz), 7.34
1
3
(
1
ꢀ
d, 2H, J = 9.0 Hz); C NMR (DMSO, 75 MHz): ı 23.8, 115.5, 121.3,
(CDCl , 75 MHz): ı 23.1, 23.3, 24.3, 28.9, 29.5, 117.9, 120.9, 129.3,
3
+
+
31.4, 153.7, 168.3; MS (ESI , m/z): 151 (33%), 109 (100); IR (neat):
133.2, 135.4, 137.6, 169.1; MS (ESI , m/z): 189 (60%), 147 (100),
119 (83); IR (neat): ꢀmax/cm 1654 (C O stretching), 1537 (NH
−
1
−1
max/cm 1640 (NH bending), 3100 (Aromatic C H).
4
ꢀ
-Methoxyacetanilide (Acros): off white crystals (69% yield,
bending), 3244 (NH stretching).
1
eluted at 40% EtOAc/Petrol); R (50% EtOAc/Petrol): 0.15; H NMR
f
(
7
1
(
1
CDCl , 300 MHz): ı 2.16 (s, 3H), 3.79 (s, 3H), 6.85 (d, 2H, J = 9.0 Hz),
3
3. Results and discussion
1
3
.38 (d, 2H, J = 9.0 Hz); C NMR (CDCl , 75 MHz): ı 24.4, 55.6, 114.0,
3
+
22.1, 131.1, 156.5, 168.7; MS (ESI , m/z): 164.91 (34%), 122.89
Initial investigation focussed on the use of methyl esters as the
acyl donor, and included both methyl benzoate and methyl pheny-
lacetate, however, in our hands, the reversibility of the reaction was
problematic wherein the methanol liberated in the CAL-B catalysed
step was more reactive than the amines being studied and thus it
−1
65), 107.82 (99); IR (neat): ꢀmax/cm 1509 (C O stretching), 1556,
604, 1644 (NH bending).
ꢀ
3
-Bromoacetanilide (Sigma–Aldrich): off white crystals (45%
1
yield, eluted at 25% EtOAc/Petrol); R (50% EtOAc/Petrol): 0.28;
H
f
NMR (CDCl , 300 MHz): ı 2.18 (s, 3H), 7.15–7.22 (m, 3H), 7.4 (d,
reacted with the acetoneoxime ester (2) giving starting ester (1)
3
13
1
1
2
H, J = 6.0 Hz), 7.76 (s, 1H); C NMR (CDCl , 75 MHz): ı 24.7, 118.5,
back again. Despite the use of 4 A˚ molecular sieves to remove the
3
+
22.7, 122.9, 127.4, 130.4, 139.3, 168.7; MS (ESI , m/z): 213 (24%),
methanol as it formed [6], the reaction could not be optimised with
methyl esters using our chosen conditions. As such, we resorted
to using vinyl acetate as an irreversible acyl donor in order to
acquire proof of principle of the proposed catalytic cycle shown
in Scheme 1. An initial screen of the amines studied can be seen in
Table 1.
−
1
15 (23), 171 (99), 173 (93), 92 (56); IR (neat): ꢀmax/cm 1538
(
C
O stretching), 1662 (NH bending), 3292 (aromatic C H).
ꢀ
4
-Bromoacetanilide (Acros): brown crystals (48% yield, eluted
1
at 20% EtOAc/Petrol); R (50% EtOAc/Petrol): 0.24; H NMR (CDCl3,
f
13
3
2
2
00 MHz): ı 2.17 (s, 3H), 7.47 (s, 4H); C NMR (CDCl , 75 MHz): ı
4.7, 117.1, 121.7, 132.1, 137.1, 168.5; MS (ESI , m/z): 213 (26%),
15 (25), 171 (99), 173 (92), 92 (40); IR (neat): ꢀmax/cm 1530
3
+
All reactions were compared to controls such that control 1
involves the direct reaction of the amine (4) with chemically syn-
thesised acetoneoxime ester (2) to determine if amide formation is
possible and worthy of further study; control 2 involves the reac-
−
1
(
C
O stretching), 1666 (NH bending), 3400 (aromatic C H).
N-(benzo[d][1,3]dioxol-5-yl)acetamide
(Sigma–Aldrich):
1
brown crystals (64% yield, eluted at 50% EtOAc/Petrol); Rf (50%
tion between vinyl acetate (1, R CH , R CH CH ) and the amine
3
2
1
EtOAc/Petrol): 0.26; H NMR (CDCl , 300 MHz): ı 2.14 (s, 3H), 5.94
(4) catalysed by CAL-B to determine the level of the background
reaction and thus gain a benchmark to observe improvements
made with the acetoneoxime catalysed reaction; and control 3
involves a one-pot reaction with all components necessary for the
proposed catalytic cycle. In the initial reactions equimolar quan-
tities of acetone oxime and the amine were used before being
reduced to catalytic amounts (0.1 equiv., 3).
3
(
s, 2H), 6.71–6.78 (m, 2H), 7.20 (s, 1H); 13C NMR (CDCl , 75 MHz):
3
ı 24.4, 101.3, 103.1, 108.3, 113.4, 132.4, 144.3, 148.0, 168.9; MS
+
−1
(
ESI , m/z): 179 (48%), 137 (99), 136 (30); IR (neat): ꢀmax/cm
1
543 (C O stretching), 1635 (NH bending), 3307 (aromatic C H).
ꢀ
4
-Methylacetanilide (Sigma–Aldrich): brown crystals (90%
1
yield, eluted at 40% EtOAc/Petrol); R (50% EtOAc/Petrol): 0.33;
H
f