Ali Ebrahimi , Akbar Heydari a,

and Ali Esrafili b a
Chemistry Department, Tarbiat Modares University, Tehran, Iran b
Department of Environmental Health Engineering, Iran University of Medical Sciences,Tehran,
Iran

Corresponding author. Tel.: +98 21 82883444; fax: +98 21 82883455.
E-mail address: heydar_a@modares.ac.ir (A. Heydari).
Table of contents
1.
Preparation and characterization of CuFe
2
O
4
2.
Assessment of the bond between the two oxides in MCO
3.
Using GC/MS for evaluating catalytic properties of MCO
4.
Characterization data of the products
5.
Determination of insertion yields by quantitative 1 H NMR spectroscopy
6.
References

1. Preparation and characterization of CuFe
2
O
4
Copper ferrite was synthesized by coprecipitation method using Cu(NO
3
)
2
.3H
2
O and
Fe(NO
3
)
3
.9H
2
O as copper and iron sources. Starting from a solution containing 0.05 M of
Copper and 0.1 M of iron, precipitation was conducted at 70 °C in an ultrasonic bath. pH was adjusted to 13 by 0.35 M NaOH solution and the slurry was stirred for an hour in the bath.
Deposits were then washed with distilled water until neutralization and filtered on Buchner funnel. After overnight drying, the hydroxide precursor was calcinated in an electrical furnace for 3 h at 700 °C to yield copper ferrite as indicated by XRD (Fig. 1). SEM of this material showed particles with average 45 nm size (Fig. 2).
Fig. 1.
XRD pattern of tetrahedral copper ferrite (CuFe
2
O
4
) obtained using Co K
α
radiation. The tiny peak at 45° is due to minor tenorite (CuO) impurity phase.
Fig. 2.
SEM image of CuFe
2
O
4 catalyst (left) and the related histogram (right)

2. Assessment of the bond between the two oxides in MCO
For checking the strength of the bond between the two oxide phases (γ-Fe
2
O
3
and CuO), some of MCO was dispersed in refluxing DCM and stirred for 24 hours. Then a magnet was used for precipitation of magnetic particles and supernatant liquid was decanted. After two extra cycles of suspending in DCM, magnet assisted precipitation and decantation, the remnant solid was used for characterization. ICP analysis of the sample showed no significant change in Cu/Fe ratio.
3. Using GC/MS for evaluating catalytic properties of MCO
Dodecane was used as an internal standard in GC experiments. For using GC to evaluate
MCO catalytic properties in the model reaction (reaction of aniline and EDA), at the beginning, calibration of peaks pertaining to aniline and its single and double N-H insertion products was performed in relation to dodecane peak. Fig. 3 shows one of the chromatograms obtained in catalyst evaluation experiments.
Dodecane
Single insertion
Double insertion
Residual aniline
Fig. 3.
Chromatogram of the reaction mixture of aniline (0.50 mmol) and EDA (0.55 mmol) in 2 ml refluxing DCM with 5 mg of MCO (2.4 mol%) after 60 min. A known amount of dodecane was added to the mixture as internal standard.
4. Characterization data of the products

H
N
O
OEt
Ethyl 2-anilinoacetate
1 H NMR (500 MHz, CDCl
3
):

1.31 (t, J = 7.2 Hz, 3H), 3.91 (s, 2H), 4.26 (q, J = 7.2 Hz, 2H), 6.66 (d, J
= 8.0, 2H), 6.79 (t, J = 8.0, 1H), 7.22 (t, J = 8.0, 2H); 13 C NMR (125 MHz, CDCl
3
):

14.2, 46.1, 61.4,
113.4, 118.6, 129.4, 146.7, 171.0; MS (EI) m/z: 51, 77, 106, 107, 179; White solid; mp 60-65 °C.
O
O
OEt
N
OEt
N , N -bis((ethoxycarbonyl)methyl)aniline
1 H NMR (500 MHz, CDCl
3
):

1.28 (t, J = 7.2 Hz, 6H), 4.15 (s, 4H), 4.23 (q, J = 7.2 Hz, 4H), 6.63 (d, J
= 8.5 Hz, 2H), 6.79 (t, J = 8.5 Hz, 1H), 7.23 (t, J = 8.5 Hz, 2H); 13 C NMR (125 MHz, CDCl
3
):

14.2,
53.6, 61.1, 112.6, 118.3, 129.3, 147.9, 171.0; MS (EI) m/z: 59, 77, 91, 106, 120, 192, 265; Colorless oil.
H
N
O
OEt
O
2
N
Ethyl 2-(4-nitroanilino)acetate
1 H NMR (500 MHz, CDCl
3
):

1.33 (t, J = 7.2 Hz, 3H), 3.98 (d, J = 4.8 Hz, 2H), 4.29 (q, J = 7.2 Hz,
2H), 5.10 (br s, 1H), 6.58 (d, J = 8.9 Hz, 2H), 8.12 (d, J = 8.9 Hz, 2H); 13 C NMR (125 MHz, CDCl
3
):

14.2, 44.9, 62.0, 111.5, 126.4, 139.0, 151.9, 169.7; MS (EI) m/z: 104, 105, 121, 151, 152, 224; Yellow solid; mp 137-139 °C.

O OEt
F O HN
NO
2
2-(ethoxycarbonyl)methylamino-2'-fluoro-5-nitrobenzophenone
1 H NMR (400 MHz, CDCl
3
): δ= 1.34 (t, J = 7.2 Hz, 3H), 4.17 (d, J = 5.4 Hz, 2H), 4.32 (q, J = 7.2 Hz,
2H), 6.67 (d, J = 9.5 Hz, 1H), 7.21 (td, J = 9.0 Hz, J = 0.8 Hz, 1H), 7.31 (td, J = 7.6 Hz, J = 1.0 Hz, 1H),
7.47 (td, J = 7.2 Hz, J = 1.8 Hz, 1H), 7.56 (m, 1H), 8.27 (dd, J = 9.2 Hz, J = 2.6 Hz 1H), 8.39 (dd, J = 2.8
Hz, J = 2.6 Hz, 1H), 9.93 (t, J = 4.7 Hz, 1H); 13 C NMR (CDCl
3
, 100 MHz): δ=14.2, 44.9, 62.1, 111.7,
116.5 (d, J = 21 Hz), 116.9, 124.7 (d, J = 3 Hz), 127.0 (d, J = 16 Hz), 129.9 (d, J = 3 Hz), 130.5, 132.1 (d,
J = 2 Hz), 133.1 (d, J = 8 Hz), 136.6, 154.0, 159.1 (d, J = 251 Hz), 168.5, 194.9; MS (EI) m/z: 109, 177,
207, 227, 273, 346; Yellow solid; mp 110-113 °C.
H
N
O
OEt
NO
2
Ethyl 2-(2-nitroanilino)acetate
1 H NMR (400 MHz, CDCl
3
):

1.32 (t, J = 7.2 Hz, 3H), 4.09 (d, J = 5.2 Hz, 2H), 4.29 (q, J = 7.2 Hz,
2H), 6.70 (dd, J = 8.8 Hz, J = 1.0 Hz, 1H), 6.70-6.75 (m, 1H), 7.44-7.48 (m, 1H), 8.29 (dd, J = 8.4 Hz, J
= 1.6 Hz, 1H), 8.41 (br t, J = 5.5 Hz, 1H); 13 C NMR (75 MHz, CDCl
3
):

14.3, 45.0, 62.0, 113.7, 116.4,
127.1, 132.9, 136.4, 144.3, 169.3; MS (EI) m/z: 77, 78, 93, 104, 105, 151, 224; IR (KBr):
 max
1735 (O-
C=O), 1623, 1513, 1247, 1154, 1027, 740, 599 cm -1 ; Yellowish orange solid; mp 82-85 °C.
Br
H
N
O
OEt
Ethyl 2-(4-bromoanilino)acetate

1 H NMR (500 MHz, CDCl
3
): δ= 1.30 (t,
J = 6.8 Hz, 3H), 3.88 (s, 2H), 4.25 (q, J = 6.8 Hz, 2H), 6.52 (d, J
= 7.3 Hz 2H), 7.29 (d, J = 7.3 Hz, 2H); 13 C NMR (CDCl
3
, 125 MHz): δ= 14.2, 45.9, 61.5, 110.5, 115.0,
132.1, 145.5, 170.7; MS (EI) m/z: 76, 104, 105, 184, 186, 257, 259; White solid; mp 97-104°C.
O
O
OEt
N
OEt
Br
N , N -bis((ethoxycarbonyl)methyl)-4-bromoaniline
1 H NMR (500 MHz, CDCl
3
): δ= 1.28 (t,
J = 7.1 Hz, 6H), 4.10 (s, 4H), 4.22 (q, J = 7.1 Hz, 4H), 6.49 (d, J
= 8.8 Hz, 2H), 7.30 (d, J = 8.8 Hz, 2H); 13 C NMR (CDCl
3
, 125 MHz): δ= 14.2, 53.6, 61.3, 110.5, 114.2,
132.0, 146.9, 170.5; MS (EI) m/z: 59, 169, 171, 184, 186, 198, 200, 270, 272, 343, 345; Pale yellow oil.
H
N
O
OEt
Ethyl 2-(4-methylanilino)acetate
1 H NMR (250 MHz, CDCl
3
):
 
1.29 (t, J = 7.5 Hz, 3H), 2.17 (s, 1H), 2.24 (s, 3H), 3.88 (s, 2H), 4.24 (q,
J = 7.5 Hz, 2H), 6.54 (d, J = 7.5, 2H), 7.01 (d, J = 7.5, 2H); White solid; mp 50-54 °C.
O
O
OEt
N
OEt
N , N -bis((ethoxycarbonyl)methyl)-4-methylaniline
1 H NMR (250 MHz, CDCl3): δ= 1.30 (t, J = 7.1 Hz, 6H), 2.27 (s, 3H), 4.15 (s, 4H), 4.24 (q, J = 7.1 Hz,
4H), 6.58 (d, J = 8.0 Hz, 2H), 7.06 (d, J = 8.0 Hz, 2H); Colorless oil.

H
N
O
OEt
MeO
Ethyl 2-(4-methoxyanilino)acetate
1 H NMR (500 MHz, CDCl
3
):

1.30 (t, J = 7.2 Hz, 3H), 3.75 (s, 3H), 3.87 (s, 2H), 4.24 (q, J = 7.2 Hz,
2H), 6.60 (d, J = 8.5, 2H), 6.80 (d, J = 8.5, 2H); 13 C NMR (125 MHz, CDCl
3
): δ= 14.2, 46.9, 55.8, 61.2,
114.4, 115.0, 141.3, 152.7, 171.4; White solid; mp 56-58 °C.
O
O
OEt
N
OEt
OMe
N , N -bis((ethoxycarbonyl)methyl)-4-methoxyaniline
1 H NMR (500 MHz, CDCl
3
):

1.26 (t, J = 7.1 Hz, 6H), 3.73 (s, 3H), 4.10 (s, 4H), 4.20 (q, J = 7.1 Hz,
4H), 6.61 (d, J = 9.1, 2H), 6.80 (d, J = 9.1, 2H); 13 C NMR (125 MHz, CDCl
3
): δ= 14.2, 54.1, 55.7, 61.0,
114.5, 114.8, 142.4, 152.7, 171.2; Oil.
H
N
O
OEt
Ethyl 2-(benzylamino)acetate
1 H NMR (400 MHz, CDCl
3
):

1.27 (t, J = 7.2 Hz, 3H), 3.41 (s, 2H), 3.81 (s, 2H), 4.19 (q, J = 7.2 Hz,
2H), 7.22-7.37 (m, 5H); 13 C NMR (100 MHz, CDCl
3
): δ= 14.2, 50.1, 53.3, 60.8, 127.2, 128.3, 128.5,
139.4, 172.4; MS (EI) m/z: 65, 91, 92, 106, 120; Colorless oil.
O
EtO
N
O
OEt

N , N -bis((ethoxycarbonyl)methyl)benzylamine
1 H NMR (400 MHz, CDCl
3
):

1.29 (t, J = 7.2 Hz, 6H), 3.59 (s, 4H), 3.96 (s, 2H), 4.19 (q, J = 7.2 Hz,
4H), 7.28 (m, 1H), 7.35 (t, J = 7.0, 2H), 7.43 (d, J = 7.0, 2H); 13 C NMR (100 MHz, CDCl
3
): δ= 14.2,
54.2, 57.8, 60.3, 127.3, 128.3, 129.0, 138.2, 171.1; MS (EI) m/z: 91, 92, 188, 206; Colorless oil.
N
O
OEt
Ethyl 2-(dibenzylamino)acetate
1 H NMR (500 MHz, CDCl
3
):

1.32 (t, J = 7.2 Hz, 3H), 3.37 (s, 2H), 3.90 (s, 4H), 4.22 (q, J = 7.2 Hz,
2H), 7.31 (t, J = 7.3 Hz, 2H), 7.39 (t, J = 7.3 Hz, 4H), 7.48 (d, J = 7.5 Hz, 4H); 13 C NMR (125 MHz,
CDCl
3
):

14.4, 53.6, 57.8, 60.2, 127.2, 128.4, 129.0, 139.1, 171.5; MS (EI) m/z: 65, 91, 92, 210, 211;
White solid; mp 63-66 °C.
O
N
O
OEt
Ethyl 2-morpholinoacetate
1 H NMR (400 MHz, CDCl
3
):

1.26 (t, J = 7.2 Hz, 3H), 2.57 (m, 2H), 3.19 (s, 2H), 3.74 (m, 2H), 4.18(q,
J = 7.2 Hz, 2H); 13 C NMR (100 MHz, CDCl
3
):

14.2, 53.3, 59.8, 60.7, 66.8, 170.1; MS (EI) m/z: 56,
70, 100, 101, 173; Colorless oil.
N
O
OEt
Ethyl 2-(4-methylpiperidino)acetate
1 H NMR (250 MHz, CDCl3): δ= 0.87 (d, J = 5.3 Hz, 3H), 1.22 (t, J = 7.2 Hz, 3H), 1.25-1.32 (m, 3H),
1.56 (d, J = 9.0 Hz, 2H), 2.08 (t, J = 11.2 Hz, 2H), 2.85 (d, J = 11.2 Hz, 2H), 3.13 (s, 2H), 4.13 (q, J = 7.2
Hz, 2H); MS (EI) m/z: 55, 69, 70, 112, 113; Colorless oil.

H
N
O
OEt
Ethyl 2-(tert-butylamino)acetate
1 H NMR (250 MHz, CDCl3): δ= 1.10 (s, 9H), 1.27 (t, J = 7.0 Hz, 3H), 1.88 (br s, 1H), 3.40 (s, 2H), 4.21
(q, J = 7.0 Hz, 2H); MS (EI) m/z: 57, 70, 71, 86, 116, 144; Colorless oil.
N
H
N CO
2
Et
Ethyl glyoxylate phenylhydrazone
1 H NMR (CDCl
3
, 500MHz): δ=1.37 (t, J = 7.2 Hz, 3H), 4.32 (q, J = 7.2 Hz, 2H), 7.00 (t, J = 7.5 Hz, 1H),
7.08 (s, 1H), 7.17 (d, J = 8.0 Hz, 2H), 7.30 (t, J = 8.00 Hz, 2H), 8.34 (broad, 1H); 13 C NMR (CDCl
3
, 100
MHz): δ= 14.3, 60.9, 114.0, 122.5, 125.9, 129.4, 142.5, 164.1; Calculated for C
10
H
12
N
2
O
2
: C, 62.50; H,
6.25; N, 14.58; Found: C, 62.29; H, 6.33; N, 14.31; Pale yellow solid; mp 129-133 °C.
O
EtO
HN
N
O
OEt
N,N -bis((ethoxycarbonyl)methyl)N' -phenylhydrazine
1 H NMR (CDCl
3
, 500MHz): δ=1.28 (t, J = 7.1 Hz, 6H), 4.14 (s, 4H), 4.22 (q, J = 7.1 Hz, 4H), 6.63 (d, J =
8.2 Hz, 2H), 6.78 (t, J = 7.3 Hz, 1H), 7.22 (m, 2H); 13 C NMR (CDCl
3
, 125 MHz): δ= 14.2, 53.5, 61.1,
112.6, 118.3, 129.3, 147.9, 171.0; Colorless oil.
N
N
O
OEt
Ethyl 2-(1-imidazolyl)acetate
1 H NMR (250 MHz, CDCl3): δ= 1.28 (t, J = 7.2 Hz, 3H), 4.24 (q, J = 7.2 Hz, 2H), 4.70 (s, 2H), 6.96 (s,
1H), 7.10 (s, 1H), 7.51 (s, 1H); Colorless oil.

EtO
2
C
N
N
H
CO
2
Et
CO
2
Et trans -3,4,5-Triethoxycarbonyl-2-pyrazoline ( trimer )
1 H NMR (CDCl
3
, 500MHz): δ= 1.28 (t, J = 7.2 Hz, 3H), 1.30 (t, J = 7.2 Hz, 3H), 1.34 (t, J = 6.9 Hz, 3H),
4.22 (q, J = 7.2 Hz, 2H), 4.24 (q, J = 7.2 Hz, 2H), 4.31 (q, J = 7.1 Hz, 2H), 4.41 (d, J = 5.4 Hz, 1H), 4.75
(d, J = 5.4 Hz, 1H), 6.83 (broad, 1H); 13 C NMR (CDCl
3
, 125 MHz): δ= 14.0, 14.1, 14.2, 52.4, 61.6, 62.2,
62.6, 66.2, 140.2, 161.3, 169.0, 169.8; White solid; mp 99-103°C.
EtO
2
C
N
N
EtO
2
C
CO
2
Et
CO
2
Et
Ethyl [1-(3, trans -4,5-tricarbethoxy-Δ 2 -pyrazoliny1)]acetate ( tetramer )
1 H NMR (CDCl
3
, 500MHz): δ= 1.26-1.35 (m, 12H), 4.16-4.35 (m, 8H), 4.45 (d, J = 10.6 Hz, 1H), 4.49
(d, J = 18.0 Hz, 1H), 4.94 (d, J = 10.6 Hz, 1H); 13 C NMR (CDCl
3
, 125 MHz): δ= 14.0, 14.1, 14.2, 14.3,
52.6, 54.1, 61.3, 61.4, 62.0, 62.3, 69.4, 136.4, 161.2, 168.3, 168.9, 169.4; Colorless oil.
5. Determination of insertion yields by quantitative 1 H NMR spectroscopy
After complete conversion of EDA as monitored by TLC, the catalyst was separated by a magnet and then the liquid was decanted. The remnant catalyst was washed two times with DCM
(2X10 ml). To the combined portions, 50 mg acetanilide was added as internal standard [1] and the mixture was passed from a short silica gel column for complete elimination of magnetic particles that could disturb NMR spectroscopy. 100 ml extra DCM was used for washing the column. The solvent was removed on rotary evaporator at reduced pressure and some residual oil or solid was used for
1
H NMR spectroscopy. The amount of single and double insertion products was determined considering the area of their NCH
2
CO
2
singlet peaks compared to acetanilide singlet peak at 2.19 ppm. Also the amount of diethyl fumarate and diethyl maleate was determined considering singlet olefinic peaks at 6.84 and 6.24 ppm respectively. For example, a spectrum relating to p-bromoaniline is shown in Fig. 4. Tiny olefinic peaks of fumarate and maleate in this spectrum correspond to less than 5% of EDA homocoupling.

CH
2
of the double insertion product
CH of diethyl fumarate
CH of diethyl maleate
CH
3
of acetanilide
CH
2
of the single insertion product
Fig. 4.
NMR spectrum from reaction mixture of p -bromoaniline and EDA with acetanilide as internal standard.
Reaction conditions: 0.50 mmol of p -bromoaniline, 0.55 mmol of EDA in 2 ml refluxing DCM with 5 mg of MCO
(2.4 mol%) and 2.5 h time.
6. References
[1] T. Rundlöf, M. Mathiasson, S. Bekiroglu, B. Hakkarainen, T. Bowden, T. Arvidsson, J. Pharmaceut. Biomed.
52 (2010) 645-651.