Catalytic activity of Mg-Al hydrotalcites and derived mixed oxides for imination reactionsviaan oxidative-dehydrogenation mechanism

Article abstract of DOI:10.1039/c9nj06096k

The catalytic activities of Mg-Al hydrotalcites and derived Mg-Al mixed oxides were studied for the imination of benzylic substrates (benzyl amine and benzyl alcohol), with aniline as a model reaction, to establish a green and cost-effective catalytic (precious metal free) process for imination and tandem reactions utilizing alcohols as reagents. The Mg-Al mixed oxide (Mg/Al ratio = 3.0) was found to be an efficient catalyst for imination reactions to synthesize cross-imines with high selectivity as well as for tandem reactions of alcohols. Basic sites of catalysts adsorb benzylic substrates through the hydrogen of their functional groups (-NH₂/-OH) and activate (weaken) benzylic C-H bonds for hydride elimination. Thus, basic sites catalyze the reaction by activating benzylic substrates for oxidative-dehydrogenation (i.e., deprotonation followed by hydride elimination with the help of oxygen) to produce reactive imine/carbonyl intermediates, which undergo subsequent nucleophilic reactions with amine.

Full text of DOI:10.1039/c9nj06096k

View Article Online
View Journal
NJC
New Journal of Chemistry
Accepted Manuscript
A journal for new directions in chemistry
This article can be cited before page numbers have been issued, to do this please use: N. Vala, P. A. Joshi
and M. Mishra, New J. Chem., 2020, DOI: 10.1039/C9NJ06096K.
Volume 42
This is an Accepted Manuscript, which has been through the
Number
6
21 March 2018
Pages 3963-4776
Royal Society of Chemistry peer review process and has been
accepted for publication.
NJC
New Journal of Chemistry
rsc.li/njc
A journal for new directions in chemistry
Accepted Manuscripts are published online shortly after acceptance,
before technical editing, formatting and proof reading. Using this free
service, authors can make their results available to the community, in
citable form, before we publish the edited article. We will replace this
Accepted Manuscript with the edited and formatted Advance Article as
soon as it is available.
You can find more information about Accepted Manuscripts in the
Information for Authors.
Please note that technical editing may introduce minor changes to the
text and/or graphics, which may alter content. The journal’s standard
Terms & Conditions and the Ethical guidelines still apply. In no event
shall the Royal Society of Chemistry be held responsible for any errors
or omissions in this Accepted Manuscript or any consequences arising
from the use of any information it contains.
ISSN 1144-2546
PAPER
Chechia Hu, Tzu-Jen Lin et al.
Yellowish and blue luminescent graphene oxide quantum dots
prepared via a microwave-assisted hydrothermal route using
H2O2 and KMnO4 as oxidizing agents
rsc.li/njc

Page 1 of 26
New Journal of Chemistry
View Article Online
DOI: 10.1039/C9NJ06096K
1
2
3
4
5
6
7
8
Catalytic activity of Mg-Al hydrotalcites and derived mixed oxides for imination
reactions via oxidative-dehydrogenation mechanism
Naresh Vala,a Pradyuman A. Joshia and Manish Mishrab,*
aDepartment of Chemical Engineering, Faculty of Technology, & Shah-Schulman Center for Surface Science
and Nanotechnology, Dharmsinh Desai University, College Road, Nadiad 387 001, Gujarat, India
bDepartment of Chemistry, Sardar Patel University, Vallabh Vidyanagar 388 120, Gujarat, India
E-mail: manishorgch@gmail.com; Tel: +91 2692 226856
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Abstract
The catalytic activity of Mg-Al hydrotalcites and derived Mg-Al mixed oxides was studied
for imination of benzylic substrates (benzyl amine and benzyl alcohol) with aniline as a
model reaction to establish a green and cost-effective catalytic (precious metal free) process
for imination and tandem reactions utilizing alcohols as reagent. The Mg-Al mixed oxide
(Mg/Al ratio=3.0) was found to be efficient catalyst for imination reactions to synthesize
cross-imines with high selectivity as well as for tandem reactions of alcohols. Basic sites of
catalyst adsorb benzylic substrates through hydrogen of their functional groups (–NH2/ –OH)
and activate (weaken) benzylic C–H bond for hydride elimination. Thus, basic sites catalyze
the reaction by activating benzylic substrates for oxidative-dehydrogenation (i.e.,
deprotonation followed by hydride elimination with the help of oxygen) to produce reactive
imine/ carbonyl intermediates, which undergo subsequent nucleophilic reaction with amine.
Keywords: Mg-Al hydrotalcites; Mg-Al mixed oxides; oxidative-dehydrogenation;
imination; tandem reactions; alcohols; imines.
1

New Journal of Chemistry
Page 2 of 26
View Article Online
DOI: 10.1039/C9NJ06096K
1
2
3
1. Introduction
4
5
6
7
8
The activation of alcohols via oxidative-dehydrogenation (under aerobic condition) to
produce reactive carbonyls is crucial step in imination and tandem reactions to trigger them
for subsequent nucleophilic reactions.1,2 Similarly, the oxidative-dehydrogenative activation
of primary amines is involved in the coupling of amines (i.e., imination reactions) to
synthesize imines.3 The heterogeneous catalysts made up of transition and noble metals have
been reported to be efficient for oxidative-dehydrogenative activation of benzylic alcohol and
amine substrates in above mentioned reactions.1-3 Hydrotalcites (HTs; layered double
hydroxide solid bases) having transition metal ions or supported noble metal nano-particles
have shown promising activity for the oxidative-dehydrogenative activation of alcohols in
imination and tandem reactions.1a,d,e,2a-c,i Basic sites of catalysts deprotonate the alcohol to
form metal alkoxide and metal-sites abstract hydride from alkoxide to produce a carbonyl
compound, which is a rate-determining step.4 In addition, supported metal nano-particles can
also activate O2 molecules by transferring electrons to reduce into superoxide or peroxygen
species for the oxidative-dehydrogenation of alcohols.4a,d
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Imination is an important reaction for the synthesis of imines, which are intermediates for the
synthesis of pharmaceuticals, agricultural chemicals, heterocyclics, fine chemicals, etc.5 In
recent years, several catalytic methods involving oxidative self coupling of primary amines
(Scheme 1a), oxidative cross coupling of two dissimilar primary amines (Scheme 1b), and
oxidative coupling of amines with alcohols (Scheme 1c) using precious metal (noble/
transition) based catalysts have been developed for the synthesis of imines.2,3,6 The
photocatalysts7 and metal free catalysts8 have also been reported for the synthesis of imines;
however, their application at large scale is difficult to practice. The Al-grafted mesoporous
silica,9 and K-10 montmorillonite10 solid acid catalysts, and alkalies11 (NaOH and KOH)
were studied to establish noble/ transition metal free catalytic methods. But the solid acid
2

Page 3 of 26
New Journal of Chemistry
View Article Online
DOI: 10.1039/C9NJ06096K
1
2
3
4
5
catalysts exhibit reduced activity due to the surface adsorption of amines on strong acidic
sites,9 and the corrosive and moisture sensitive alkalis are difficult to handle at large scale.
6
7
8
9
Catalyst, [O]
(a)
(b)
(c)
H N
R
2
R
N
R
2
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Catalyst, [O]
Catalyst, [O]
R
R
R'
N
N
R NH2
R NH2
H2N R'
HO R'
+
R'
+
Scheme 1. Methods for synthesis of imines by catalytic oxidative (a) self coupling of a
primary amine, (b) cross coupling of two dissimilar primary amines, and (c) cross coupling of
an amine with an alcohol.
The cross-imines or unsymmetrical imines (R≠Rʹ) are of great importance in organic
synthesis,12 which can be synthesized by imination of an amine or alcohol substrate with an
amine (Scheme 1b & 1c). The selectivity of cross-imines is a major concern, especially in
cross-coupling of two dissimilar primary amines (Scheme 1b), as the self-coupling and the
side reactions (which produce by-products such as nitriles, carbonyls, amides, azo
compounds, etc.) reduce the selectivity of cross-imines.3,8 The imination of alcohols with
amines (Scheme 1c) is of great interest for the selective synthesis of cross-imines,2,11 using
alcohols as naturally abundant and inexpensive chemicals, which produce only hydrogen or
water as co-product. To activate the alcohols for this reaction, the transition or noble metal
based heterogeneous catalysts have been extensively used.2
The precious metal free catalysts with potential to activate the alcohol and amine substrates
for oxidative-dehydrogenation are promising to establish cost-effective methodology for
imination and tandem reactions. Therefore, we studied the catalytic activity of as-synthesized
Mg-Al HTs (with Mg/Al ratio of 2 and 3) and derived Mg-Al mixed oxide for imination of
benzyl alcohol and benzyl amine with aniline (Scheme 1b&1c) as a model reaction. Mg-Al
3

New Journal of Chemistry
Page 4 of 26
View Article Online
DOI: 10.1039/C9NJ06096K
1
2
3
4
5
6
7
8
9
mixed oxide (with Mg/Al ratio of 3) showed excellent activity in imination to synthesize
cross-imines as well as in tandem reactions of alcohols. Here, we wish to report that the
surface basic sites, without help of metal sites, are capable to activate alcohol substrates for
oxidative-dehydrogenation in imination and tandem reactions.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
2. Experimental
2.1. Materials
All the chemicals were used of synthetic grade having purity above 99%, and were used
without any further purification. The Mg(NO3)2·6H2O, Al(NO3)3·9H2O, NaOH and Na2CO3
were procured from S.D. Fine Chemicals Ltd., India. The amines, alcohols, acetophenone,
cyclohexanone and malononitrile were purchased from Merck India Ltd.
2.2. Synthesis of Mg–Al hydrotalcite and Mg–Al mixed oxide samples
The Mg–Al HTs with the degree of partial substitution of Mg2+ by Al3+ in the range of 0.2–
0.34 (i.e., Mg/ Al molar ration of 5 to 3) exist in pure phases of hydrotalcites.13 Furthermore,
the HTs derived mixed oxide catalysts with Mg/Al ratio of ~ 2 to 3 have been demonstrated
to show high activity in many reactions.14 Therefore, Mg-Al HTs with Mg/ Al molar ratio of
2 and 3 and their derived Mg-Al mixed oxides were synthesized. The HT samples with Mg/
Al molar ratio of 2 and 3 were synthesized by a co-precipitation method at constant pH.15 An
.
.
aqueous solution (called A) of Mg(NO3)2 6H2O and Al(NO3)3 9H2O in the desired Mg2+/ Al3+
molar ratio was prepared in 200 mL double distilled deionized water. The solution A was
added drop wise into a second solution (B) containing mixture of NaOH (0.72 mol) and
Na2CO3 (0.21 mol) in 200 mL double distilled deionized water, in around 2 h under vigorous
stirring at room temperature. The content was then aged at 70°C for 14 h. After 14 h, the
precipitate formed was filtered and washed thoroughly with hot distilled water until pH of the
4

Page 5 of 26
New Journal of Chemistry
View Article Online
DOI: 10.1039/C9NJ06096K
1
2
3
4
5
6
7
8
9
filtrate was 7. The washed precipitate was then dried in an oven at 80°C for 14 h, which gave
Mg–Al hydrotalcite (HT). The hydrotalcites with Mg/ Al ratio of 2 and 3 were labelled as
HT-2 and HT-3, respectively. The thermogravimetric (TGA-DTG) study of the HTs (Figure
S1) showed significant weight loss in the temperature range of 300°C to 550°C attributed to
loss of hydroxyls of Brucite layer, interlayer carbonate and hydroxyl ions. Therefore, the HT-
2 and HT-3 were calcined at 520°C for 4 h to prepare their Mg–Al mixed oxides (AHTs),
which were named as AHT-2 and AHT-3, respectively.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
2.3. Characterization of Mg–Al hydrotalcite and Mg–Al mixed oxide samples
The Mg/Al molar ratio in the synthesized samples was estimated by inductively coupled
plasma atomic emission spectroscopy (ICP-AES; Perkin Elmer Instrument, Optima 200 DV).
The sample (100 mg) was dissolved in 40% HF solution (15-20 drops) followed by addition
of 5 wt.% boric acid solution making up to 100 mL in volumetric flask, which was analyzed
by ICP. The Brunauer-Emmett-Teller (BET) surface area of the samples, degassed at 110ºC
for 2 h under vacuum, was measured from N2 adsorption-desorption isotherm study at liquid
nitrogen temperature (77 K) using Quantachrome NOVA 1000e surface area analyzer. The
X-ray diffraction study of the samples was carried out on Bruker, Advanced D8, using Cu Kα
radiation (λ = 1.5418 Å) and Lynx Eye detector, scanning the samples in 2θ range of 10 to
80° with a scanning rate of 0.02º s-1. Fourier transform infrared (FTIR) spectra of samples
were recorded by FTIR spectroscopy (IRPrestige-21, Shimadzu) using a Diffuse Reflectance
Scanning disc technique, mixing the sample with dried KBr, in the wavelength range of 400–
4000 cm-1. Thermo gravimetric analysis (TGA) of HT samples were carried out using Mettler
Thermal Analyser (TGA/DSC 1 SF/752) by heating the sample in the range of 50 to 800°C
1
with a heating rate of 10°C min- under nitrogen flow (50 mL min-1). Temperature
programmed desorption of CO2 (CO2 TPD) and NH3 (NH3 TPD) for the samples were carried
5

New Journal of Chemistry
Page 6 of 26
View Article Online
DOI: 10.1039/C9NJ06096K
1
2
3
4
5
6
7
8
9
out using Micromeritics, USA. The sample (50 mg) was preheated at 100°C for 1 h under
helium flow (30 mL h-1). The CO2/ NH3 was adsorbed on the samples at 50°C by exposing to
a flow of helium mixed CO2/ NH3 gas (10%, 20 mL h-1) for 1 h. The desorption of CO2/ NH3
was performed by heating the sample up to the final temperature of 800°C (12°C min-1) and
was measured by gas chromatography with thermal conductivity detector (TCD).
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
2.4. Evaluation of catalytic activity of samples
For the evaluation of catalytic activity of samples in imination of benzyl amine (1a) or benzyl
alcohol (1b) with aniline (2) (Scheme 2), the mixture of 1a or 1b and 2 along with the
catalyst was taken in a 50 mL reaction tube of reaction station (12 Place Heated Carousel
Reaction Station, RR99030, Radleys Discovery Technologies, UK). The reaction was carried
out at desired temperature under stirring for required reaction time. The reactions were
carried out either in the presence of air (atmospheric oxygen; aerobic condition) by keeping
the vessel (reaction tube) open or in the closed vessel flushed with nitrogen (aerobic
condition). After the reaction, the reaction mixture was cooled and diluted with
dichloromethane (5 mL). The catalyst was separated from reaction mixture by filtration.
NH2
or
OH
NH2
N
+
HTs/ AHTs
(3)
(1a)
(1b)
(2)
Scheme 2. Imination of 1a or 1b with 2 using HTs and AHTs.
The catalyst showing highest activity in above reactions was also studied for the imination of
different derivatives of 1a and 1b with different amines, and the tandem reactions of 1b with
different substrates (acetophenone, cyclohexanone and malononitrile) under the condition
optimized for imination of 1a and 1b with 2. The reaction mixtures were analyzed by gas
6

Page 7 of 26
New Journal of Chemistry
View Article Online
DOI: 10.1039/C9NJ06096K
1
2
3
4
5
6
7
8
9
chromatography (Agilent 5975) having a HP-5 (60 meter) capillary column with a
programmed oven temperature from 50 to 280ºC, a 0.5 cm3/min flow rate of N2 as carrier gas
and FID detector. The conversion of substrates (1a, 1b and their derivatives) was calculated
on the basis of their mole percent as given below;
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Conversion = 100 X [Initial mole % of substrate – Final mole % of substrate]/ Initial mole %
of substrate.
All the conversion values reported are within ±2% precision.
The selectivity of the product was calculated as below,
Selectivity (%) = 100 X peak area of product/ Ʃ Total peak area for all the products.
The products and by-products formed in the reactions were characterized by GC–MS analysis
and the data were matched with those reported in the literature. GC–MS analysis was carried
out using gas chromatograph mass spectrometer (Agilent 5975C GC/MSD with 7890A GC
system) having HP-5 capillary column of 60 m length and 250 µm diameter with a
programmed oven temperature from 50 to 280°C, at 1 mL min−1 flow rate of He as carrier gas
and ion source at 230°C.
3. Results and discussions
3.1. Characteristics of HT and AHT samples
From the ICP-AES elemental analysis, the Mg/Al atomic ratio in HT-2 and HT-3 were found
to be 1.9 and 2.6, respectively. The significant reduction in Mg/Al ratio in the HT-3 as
compared to the targeted Mg/Al ratio of 3.0 may be due to the loss of magnesium as
Mg(OH)2, which is more water soluble as compared to Al(OH)2. The BET surface area of the
synthesized HT-2 and HT-3 were 76 m2/g and 72 m2/g, respectively, which were increased
for mixed oxides, i.e., the AHT-2 and AHT-3 (195 m2/g and 158 m2/g, respectively).
7

New Journal of Chemistry
Page 8 of 26
View Article Online
DOI: 10.1039/C9NJ06096K
1
2
3
4
5
(iv)
(b)
(a)
6
7
8
9
1667
1498
838
666
(iv)
3016
3605
3585
1420
(iii)
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
1660
1482
837
661
3012
(iii)
(ii)
(i)
1412
(ii)
1665
1488
1377
627
932
3015
3008
733
3542
3427
(i)
545
1665
1530
1365
656
936
781
4000 3500 3000 2500 2000 1500 1000 500
-1
10
20
30
40
50
60
70
80
Wave number (cm
)
2
Figure 1. (a) XRD patterns and (b) FTIR spectra of samples [(i) HT-2, (ii) HT-3, (iii) AHT-2
and (iv) AHT-3].
The powder XRD patterns of HTs and their mixed oxides (AHTs) are shown in Figure 1a.
2-
The presence of CO3 anions in the interlayer gallery of HTs is confirmed by the
characteristic basal spacing d003=7.65A°. The sharp and symmetric basal reflections of (003)
and (006) planes at low 2θ values (11.5 to 23.4°) and broad asymmetric reflections at higher
2θ values (30 to 50°) indicate highly crystalline layered structure of HTs.16 The calcination of
HTs at 520°C gave a uniform mixed oxide phase of Mg(Al)Ox in AHTs showing diffraction
lines very similar to that of MgO.
The FTIR spectra of the synthesized HT-2 and HT-3 (Figure 1b) show characteristic bands
of Mg–Al hydrotalcite.17 The broad band ranging from 4000–3000 cm−1 is attributed to the
stretching vibration of structural hydroxyl (–OH) groups of the Brucite-like layer. This band
is slightly shifted towards higher frequency for HT-3 as compared to that in HT-2, which can
be due to the major contribution by Mg–OH. The shoulder at ~3000 cm−1 represents
8

Page 9 of 26
New Journal of Chemistry
View Article Online
DOI: 10.1039/C9NJ06096K
1
2
3
4
5
6
7
8
9
hydrogen bonding between water molecules and interlayer carbonate anions (CO32−). A sharp
band centred at 1360–1380 cm−1 is attributed to symmetric O–C–O stretching of carbonate
anions present in interlayer space in HTs.18 The weak bands at 1530 cm-1 and 1665 cm-1 in
FTIR spectrum of HT-2 are asymmetric O–C–O stretching of carbonate ions and asymmetric
O–C–O stretching of bicarbonate ions, respectively.19 In FTIR spectrum of HT-3, the weak
bands at 1488 cm-1 and 1665 cm-1 are ascribed to symmetric and asymmetric O–C–O
stretching of interlayer bicarbonate.19 The bands appeared below 1000 cm−1 is ascribed to
carbonate and M–OH modes.18 The FTIR spectrum of AHT-2 and AHT-3 (Figure 1b) shows
slightly shifted band for stretching of hydroxyl groups (4000–3000 cm-1) towards higher
frequency with decreased intensity as compared to HTs indicating presence of strongly
associated hydroxyls and water molecules with metals (Mg and Al) of mixed oxide. The
peaks (in the range of 1360 cm-1 to 1670 cm-1) representing the carbonate and bicarbonate
species on oxide surface19 can also be seen with shifted peak positions indicating the change
in their symmetry.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
The acidity and basicity of the samples in terms of concentration and strength of sites,
measured by NH3 TPD and CO2 TPD analysis, respectively, are summarized in Table 1
(Figure S2 & S3). The HT-2 possesses stronger acidic sites than HT-3, and AHT-2 has
higher acidity (number of acidic sites) than AHT-3 due to more Al content. The HT-3 and
AHT-3 possess higher basicity (amount and strength) than HT-2 and AHT-2. The basicity of
HTs is mainly due to their OH- groups which act as week Bronsted basic sites. Cosimo et
al.,20 reported that the nature, strength and density of surface basic sites in mixed oxides
depended on the Al content. They found that the increase in Al content in MgO i.e., in mixed
oxides, reduced the basic sites density of low and medium strength basic sites and increased
the acid site density.
9

New Journal of Chemistry
Page 10 of 26
View Article Online
DOI: 10.1039/C9NJ06096K
1
2
3
4
5
6
7
8
9
The calcination of HTs into AHTs greatly increased the basicity. The mixed oxides obtained
from calcination of hydrotalcite are higher in basicity compared to as-synthesized
hydrotalcites, both in terms of number of basic sites and strength.20 The calcination of HTs at
520°C results to a well-dispersed mixture of magnesium and aluminium oxides, i.e., AHTs,
which possess strong basicity due to surface OH- groups (Bronsted basic sites of low
strength), Mg–O pairs (Lewis basic sites of medium strength), and O2- anions (strong Lewis
basic sites).17,19 The amount of medium and stronger Lewis basic sites is higher as compared
to weaker Bronsted sites in AHTs. The acidity of Mg-Al mixed oxides is due to aluminium
oxide (Al3+ cations). The increased acidity of AHT-2 as compared to HT-2 can be attributed
to significant amount of accessible Al3+ cations in Mg-Al mixed oxide exhibiting Lewis
acidic nature. However, AHT-3 did not show enhancement in acidity as compared to HT-3.
The calcination of HT-3 gives a MgO rich mixed oxide, which may have less amount of
accessible Al3+ cations to show increased acidity. The MgO rich mixed oxides with less
Al2O3 content have been observed to possess less density of acidic sites.20
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Table 1. Concentration and strength of acid and basic sites in HTs and AHTs.
Basic sites concentration & strength
Acid sites concentration & strength
Amount
Sample
HT-2
Temp.
(°C)
Amount
(mmol CO2/ g)
Total (mmol Temp.
Total (mmol
NH3/ g)
(mmol
NH3/ g)
0.57
CO2/ g)
(°C)
168
0.66
0.66
420
0.57
186
602
1.15
1.78
HT-3
2.93
5.21
122
0.72
0.72
123
218
387
0.36
0.16
4.69
133
218
386
0.15
0.29
5.72
AHT-2
AHT-3
6.16
0.71
190
327
587
1.06
7.78
2.17
11.01
448
0.71
10

Page 11 of 26
New Journal of Chemistry
View Article Online
DOI: 10.1039/C9NJ06096K
1
2
3
3.2. Catalytic activity of HTs and AHTs in imination of 1a and 1b with 2
4
5
6
7
8
The equimolar reaction of 1a or 1b with 2 using HTs and AHTs (Scheme 2; 10 mmol 1a/ 1b,
10 mmol 2, 100 mg catalyst, 12 h) under anaerobic or aerobic conditions, gave highest
conversion at 180°C than at lower and higher temperatures (170°C and 190°C, respectively).
This shows that 180°C is optimum temperature for both the imination reactions. The
imination of 1a with 2 at 180°C (Scheme 3) was studied with HTs and AHTs under
anaerobic and aerobic conditions. The higher conversion of 1a in aerobic reactions than
anaerobic reactions (Figure 2a) indicates that O2 is essential for the reaction. There was no
conversion when aerobic reaction of 1a or 1b with 2 was carried out at 180°C in absence of
the catalyst. This shows that O2 do not directly react with reactants to catalyze the reaction;
the reaction takes place with the help of a catalyst and O2. The anaerobic reactions did not
produce desired product (i.e., cross-imine; 3) and gave 100% self-imine (4). The aerobic
reactions gave substantial amount of 3 after 48 h along with by-products (Figure 2b). HT-3
and AHT-3 gave faster conversion of 1a than HT-2 and AHT-2, respectively, in aerobic
reactions (Figure 2a), and the mixed oxides (AHT-2 and AHT-3) gave slightly higher
conversion of 1a than their respective HTs. Thus, AHT-3 showed highest activity under
aerobic condition giving faster conversion of 1a and highest selectivity of 3 (99% conversion
of 1a with 81% 3 and 19% by-products after 48 h).
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
NH
2
NH
2
Catalyst (100 mg)
180C
N
N
+
+
(1a)
(3)
(4)
(2)
10 mmol
10 mmol
Scheme 3. Imination of 1a with 2 using HTs and AHTs into cross-imine (3) & self-imine (4).
The product 3 is produced from 4 by its trans-imination (nucleophilic reaction) with 2,21
which is also evident from the reaction kinetics showing increasing selectivity of 3 and
11

New Journal of Chemistry
Page 12 of 26
View Article Online
DOI: 10.1039/C9NJ06096K
1
2
3
4
5
6
7
8
9
decreasing selectivity of 4 with time (Figure 2b). We confirmed that the by-products
produced in aerobic reactions are also produced from 4 by its base catalyzed reactions with
1a (see ESI). This shows that the conversion of 4 into by-products reduces the selectivity of
3. The increase in molar amount of 2 (from 10 mmol to 20 mmol) in the aerobic imination of
1a with AHT-3 increased the selectivity of 3 (90%) in 24 h and reduced the amount of by-
products (6%). The use of excess amount of 2 (20 mmol) will enhance the nucleophilic attack
with 4 speeding up the formation of 3 and suppressing the side reactions, and therefore, gives
high selectivity of 3 with faster rate.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
100
80
60
40
20
0
100
(b)
(a)
80
60
40
20
0
In anaerobic
condition
In aerobic
condition
6
12 18 24 30 36 42 48
Reaction time (h)
6
12 18 24 30 36 42 48
Reaction time (h)
Figure 2. (a) Conversion of 1a in anaerobic and aerobic imination of 1a with 2 at 180°C
using HTs and AHTs [■: HT-2; ●: HT-3; : AHT-2; : AHT-3], and (b) selectivity of
products in aerobic reactions [3: blue dotted line; 4: red dotted line; by-products: pink dotted
line; the by-products were characterized by GC-MS (see ESI); there was 100% 4 in anaerobic
reactions].
The aerobic condition was also helpful for HTs and AHTs catalyzed imination of 1b with 2
giving higher conversion of 1b than anaerobic reactions (Table 2). The HT-3 and AHT-3
were more active giving higher conversion of 1b than HT-2 and AHT-2. As compared to
amine coupling reactions (i.e., imination of 1a and 2), the imination of an alcohol (1b) with
amine (2) gave high selectivity of 3 (98%) showing that alcohol substrates are suitable
12

Page 13 of 26
New Journal of Chemistry
View Article Online
DOI: 10.1039/C9NJ06096K
1
2
3
4
5
6
7
8
9
iminating reagent for selective synthesis of cross-imines. In both the imination reactions, the
substrates (1a and 1b) undergo either dehydrogenation (in anaerobic reactions) or oxidative-
dehydrogenation (in aerobic reactions) followed by nucleophilic reaction with 2.2,3 The study
reveals that the HTs and AHTs have poor dehydrogenation activity (less activity in anaerobic
reactions) but exhibit good oxidative-dehydrogenative activity giving higher conversion of 1a
and 1b in aerobic imination reactions.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Table 2. Catalytic activity of HTs and AHTs in imination of 1b with 2.
OH
NH
2
Catalyst (100 mg)
180C
N
+
(3)
(1b)
(2)
10 mmol 10 mmol
Catalyst Reactn time
Anaerobic reaction
Aerobic reaction
Conv. (%) of
1b
(h)
Conv. (%) of
1b
Select. (%)
3
Select. (%)
Othersa
3
97
98
98
98
92
91
98
100
99
98
Othersa
HT-2
HT-3
24
48
24
48
24
48
24
31
21
35
28
6
97
87
97
91
95
94
93
3
13
3
55
70
51
88
57
72
72
80b
78c
90
3
2
2
2
8
9
2
-
9
5
6
7
AHT-2
AHT-3
30
2
1
2
48
21
87
13
aOthers: benzaldehyde.
bReaction carried out using 20 mmol of 1b.
cThird cycle reuse using 20 mmol of 1b.
The reported heterogeneous catalysts for imination of alcohols are mostly precious metals
based, and are active in presence of a solvent and/or a base additive (Table 3).2a-g AHT-3 is
an inexpensive catalyst and gives similar conversion of 1b and selectivity of 3 under solvent
free condition and without use of any base additive. In addition, the higher activity of AHT-3
than the reported catalysts is clearly evident from Table 3; AHT-3 showed activity at much
lower amount (1b/ catalyst weight ratio = 10, i.e., 10 wt.%) under solvent free condition,
13

New Journal of Chemistry
Page 14 of 26
View Article Online
DOI: 10.1039/C9NJ06096K
1
2
3
4
5
6
7
8
9
whereas, the reported catalysts were active at much higher amount (e.g., 1b/ catalyst weight
ratio = 2.0 to 0.2) and in presence of non-polar solvents (aromatic hydrocarbons). The
equimolar reaction of 1b and 2 under aerobic condition with AHT-3 using a higher amount of
catalyst (at 1b/ catalyst wt. ratio of 2.0) in presence of a solvent (mesitylene; 5 mL) gave
reduced conversion (40% after 24 h). Unlike reported catalysts, more amount of catalyst
(AHT-3) and presence of solvent showed detrimental effect on the reaction. This can be
attributed to poor dispersion of large amount of catalyst (AHT-3) in reaction mixture
reducing catalyst’s activity.22 The reduced activity of catalyst in the presence of solvent may
be due to slow diffusion of the reactant molecules through the bulk solvent.23
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Table 3. Comparison of catalytic activity of AHT-3 and reported heterogeneous catalysts for
imination of 1b with 2.
Select./
Conv.
(%) of
1b
1b/catalyst Temp. Time
yield
(%)
of 3
98, 91i
97i
Entry
Catalyst
Solvent
wt. ratio
(°C)
(h)
1a
2b
3c
4d
5e
6f
AHT-3
Fe doped HT
MnOx/HAP
Au/HAP
CeO2
K-OMS-2
10
0.2
0.8
0.77
2.0
2.0
180
110
80
60
60
48
24
24
3
24
24
-
90
-
xylenes
toluene
toluene
mesitylene
toluene
ethyl-
99
99
-
93
99
96i
110
100
100
7g
8h
Pt-Sn/γ-Al2O3
0.2
-
138
160
24
12
99
-
99
94i
benzene
-
TiO2@PMHSIPN
a100 mg, 10 mmol 1b, 10 mmol 2, O2.
b100 mg, 0.24 mmol 1b, 0.29 mmol anisidine, 3 mL xylenes.2a
c125 mg, 1 mmol 1b, 1 mmol 2a, 2 mL toluene, air.2b
d130 mg, 1 mmol 1b, 1 mmol 2, 10 mL toluene, 60°C, O2.2c
e50 mg, 1 mmol 1b, 2 mmol 2, 1.5 g mesitylene, 60°C, air.2d
f50 mg, 1 mmol 1b, 2 mmol 2a, 10 mL toluene, 110°C, air.2e
g120 mg, 1 mmol 1a, 1 mmol 2a, 2 mL ethyl benzene, 138°C, O2.2f
h2 mol% Ti, 20 mol% K2CO3, 1 mmol 1b, 0.2 mmol 2, 160°C, argon.2g
iIsolated yield.
Recently, the transition metal ions (Fe3+, Zn2+, Ni2+, Cr3+, Cu2+) doped HTs and Pd0
supported on doped HT catalysts were studied for catalysis of dehydrogenation and imination
of alcohols.2a The Pd0 supported on doped HT catalysts showed good activity for alcohols’
dehydrogenation, however, exhibited reduced activity for imination due to Pd0. Furthermore,
14

Page 15 of 26
New Journal of Chemistry
View Article Online
DOI: 10.1039/C9NJ06096K
1
2
3
4
5
6
7
8
9
the spent catalyst (Fe3+ doped HT) showed significant loss in activity and was washed with
aqueous K2CO3 to restore the activity. We studied the reusability of the spent AHT-3 catalyst.
The spent catalyst recovered from reaction mixture by filtration was dried and used without
any treatment in the reaction of 1b with 2 for three consecutive reaction cycles under similar
reaction condition. The spent catalyst did not give significant reduction in conversion and
selectivity after third cycle (Table 2), which shows that spent AHT-3 is reusable.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
3.3. Role of surface basic sites in catalysis of imination reactions
The adsorption of benzylic compounds, having –XH functional group (X = NH and O, i.e.,
1a and 1b, respectively), on silica surface has been proposed to be a bifurcated interaction
between –XH and surface acidic-basic sites;24 X and H interact with acidic and basic sites,
respectively. The adsorption of 1a and 1b on HTs and AHTs can occur either by a bifurcated
interaction between –XH and surface acidic-basic sites (Scheme 4a) or by an interaction of H
with only basic sites (Scheme 4b). As the proportion of basic sites is higher than acidic sites
in HTs and AHTs, the adsorption of 1a and 1b will be predominantly on basic sites (Scheme
4b). The adsorption behavior of HTs and AHTs for 1a and 1b were studied at room
temperature (see ESI). The highest adsorption of 1a and 1b on AHT-3 (Table S1), a highly
basic catalyst, shows that the adsorption occurs mainly on basic sites.
-
-
Ph
Ph
Ph
H
(a)
Ph
H
(b)
(c)
(d)
CH2
X
CH2
X
CH
X
CH
X
+
+
H
B
H
B
H
H
A
A
B
B
A = acid site, B = basic site
X = NH/ O
Scheme 4. Adsorption of a benzylic substrate on HTs/ AHTs over (a) acidic-basic sites, (b)
only surface basic site, and (c & d) formation of respective adsorbed species.
15

New Journal of Chemistry
Page 16 of 26
View Article Online
DOI: 10.1039/C9NJ06096K
1
2
3
4
5
6
7
8
9
The adsorbed species were characterized by FTIR analysis of 1a and 1b adsorbed samples
(ESI). FTIR spectra of 1a and 1b adsorbed samples exhibit shifting of CH2 scissoring to a
lower frequency (as compared to neat 1a and 1b; Figure S4 & S5) and intense peaks for H–
C–H in-plane and out of plane vibrations. This indicates the weakened benzylic C–H bonds
in adsorbed species, which is possibly due to polarization of C–H bond as C+–H-. Thus, the
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
adsorbed species of 1a and 1b are proposed to possess polarized benzylic C–H bonds as C+–
H- with partial double bond character in C–N and C–O moieties, respectively (Scheme 4c &
4d). The partial deprotonation of 1a and 1b (–NH2 and –OH, respectively) by basic sites can
cause polarization of benzylic C–H bonds as C+–H-. The adsorption of fluorinated ethanols
on oxidized Cu and Ag surfaces has been reported to produce surface adsorbed deprotonated
species (fluorinated ethoxides), which possess C–H bonds polarized as C+–H-.25 The study
reveals that adsorption/ interaction of 1a and 1b through their functional group’s hydrogen on
surface basic sites of HTs or mixed oxides weakens the benzylic C–H bonds. The adsorbed
species of 1a and 1b can eliminate benzylic hydride (H) under thermal condition during the
reaction to produce imine-/ carbonyl reactive intermediate (Scheme 5a). The adsorbed
fluorinated ethoxides on oxidized Cu and Ag surfaces were observed to undergo thermal
decomposition by eliminating H– to yield fluorinated acetaldehydes.25 The basic sites of
HTs/ AHTs not only help in the deprotonation of substrates but also activate the benzylic
position for H– elimination. The H+ on basic site may combine with H– ion to form H2,
however, this seems to be a slow process with HTs and AHTs showing poor dehydrogenative
activity in anaerobic reactions. The higher conversion of benzylic substrates in aerobic
reactions suggests that O2 plays important role as an oxidant/ hydrogen acceptor to efficiently
accept H– and H+ ions speeding up the reaction. The O2 molecules accept eliminated H– ions
and gets reduced into peroxide (–O–OH) ions, which can react with H+ abstracted by basic
site to form H2O2 (Scheme 5a).26 The imine-intermediate reacts with 1a to form 4, which
16

Page 17 of 26
New Journal of Chemistry
View Article Online
DOI: 10.1039/C9NJ06096K
1
2
3
4
5
6
7
8
undergo nucleophilic reaction with 2 to form 3 (Scheme 5b).9,10 Similarly, the carbonyl
intermediate formed by oxidative-dehydrogenation of 1b can also react with 2 to form 3
(Scheme 5c).
9
The metal sites in transition or noble metal based catalysts act as redox or strong Lewis acidic
sites to abstract a / benzylic hydrogen as H–.2a-i,4 The Ti-sites in organosilicon-supported
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
titania (TiO2@PMHSIPN) have been proposed to be active sites for abstraction of H– during
dehydrogenation of alcohol.2g However, HTs and AHTs do not have such metal sites for
abstraction of benzylic H–. Gellman and Dai reported H– elimination from adsorbed
alkoxides on oxidized Cu and Ag surfaces by thermal decomposition to yield aldehydes.25
The benzylic H– elimination from adsorbed species on HTs and AHTs may also occur by
thermal decomposition, therefore a higher temperature (180°C; as compared to reported
catalysts) is required for HTs and AHTs catalyzed imination reactions (Table 3).
(a)
Oxidative-dehydrogenation of substrate (1a/ 1b)
Ph
-
H
Ph
Ph
H-X
O2
Imine-/ carbonyl-
intermediate
(1a/ 1b)
+
X
X
H
B
Adsorption
B
B
H2O2
HT/ AHT surface
(II)
(I)
B : basic site,
X : NH/ O
Trans-imination
(b)
Ph NH2
H2N
Ph
(1a)
(2)
Ph
Ph
Ph
N
Ph
N
Ph
-NH3
NH
Ph
H2N
(3)
(4)
Imine-
intermediate
(c)
Ph NH2
Ph
(2)
Ph
N
Ph
-H2O
O
(3)
Carbonyl-
intermediate
Scheme 5. The plausible mechanism of AHT-3 catalyzed imination reactions.
17

New Journal of Chemistry
Page 18 of 26
View Article Online
DOI: 10.1039/C9NJ06096K
1
2
3
4
5
6
7
8
9
We confirmed that the trans-imination of 4 with 2 (Scheme 5b) and the reaction of carbonyl
intermediate, i.e., benzaldehyde with 2 (Scheme 5c) are non-catalytic steps. The equimolar
reactions of 4 (10 mmol) with 2 (10 mmol), and benzaldehyde with 2 (10 mmol) at 180°C in
absence of catalyst gave complete conversion (of 4 and benzaldehyde) into 3 within 4 h. This
shows that the catalyst is mainly involved in base catalyzed oxidative-dehydrogenation of
substrates to produce imine/ carbonyl reactive intermediate.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
The catalytic activity of HTs and AHTs can be related with their surface basicity. The higher
activity of AHT-3 than other catalysts (Figure 2 & Table 2) is attributed to its highest
basicity (11.01 mmol CO2/ g; Table 1), which can promote the reaction by adsorbing and
activating more molecules of benzylic substrates (1a/ 1b) for dehydrogenation to produce
imine/ carbonyl intermediates. The highest selectivity of 3 with AHT-3 in imination of 1a
with 2 (Figure 2b) can also be attributed to higher basicity giving faster conversion of 1a into
4 and producing more molecules of 4 for trans-imination to yield 3. This can be noticed that
even though AHT-2 possesses higher basicity than HT-3 (Table 1), but AHT-2 gives slower
conversion of 1a and 1b (Figure 2a & Table 2) as well as lesser selectivity of 3 in imination
of 1a (Figure 2b). This can be ascribed to high surface acidity, which can strongly bind
amines (1a and 2) and intermediate (4) slowing down the reaction.9
3.4. Scope of AHT-3 in imination and tandem catalysis
The catalytic activity of AHT-3 was evaluated for imination of different benzylic substrates
(amines/ alcohols) with different amines under similar reaction conditions (Table 4). The
AHT-3 showed excellent activity with all the substrates and amines giving good conversion
and selectivity of cross-imines. However, in some of the reactions conversion of substrate or
selectivity of cross-imine was less, which was attributed to the substituents present in the
benzylic substrate or amines affecting the reactivity. For example, the electron donating
18

Page 19 of 26
New Journal of Chemistry
View Article Online
DOI: 10.1039/C9NJ06096K
1
2
3
4
5
6
7
8
9
group (–OCH3) in a benzylic amine substrate (Table 4; entry 2) was responsible for less
selectivity of cross-imine product (12%). The electron donating group will enhance the
nucleophilicity of amine substrate giving efficiently self-imine product. However, the self-
imine product will be less reactive towards trans-imination (with aniline) due to reduced
electrophilicity of the carbon of C=N group by resonance effect of –OCH3 giving less
selectivity of cross-imine product. The selectivity of the cross-imines could be enhanced (to
90%) by using excess molar amount of amine (40 mmol; Table 4; entry 2).
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Table 4. Conversion and selectivity in AHT-3 catalyzed imination reactions of different
benzylic substrates and amines.
Selectivity (%)
Conv. (%) of
benzylic
substrate
Benzylic amine/
alcohol substrate
NH2
Entry
Amine
Cross-
imine
Self-
imine
NH2
1
2
99
90
3
NH2
NH2
96
12, 90a
88, 10a
OCH3
NH2
NH2
NH2
3
4
97
70
92
30
8
NO2
NH2
100
OCH3
NH2
NH2
5
6
100
80
70
30
-
NO2
NH2
OH
OH
100
NH2
7
8
50, 90b
95
100
100
-
-
OCH3
OH
NH2
NH2
NO2
OH
9
82
80
100
100
-
-
OCH3
NH2
OH
10
NO2
Entry 1 to 5: 10 mmol benzylic substrate, 20 mmol amine, 100 mg AHT-3, 180°C, 24 h, air.
Entry 6 to 10: 20 mmol benzylic substrate, 10 mmol amine, 100 mg AHT-3, 180°C, 24 h, air.
aUsing 40 mmol amine.
bAfter 48 h.
19

New Journal of Chemistry
Page 20 of 26
View Article Online
DOI: 10.1039/C9NJ06096K
1
2
3
4
5
6
7
8
9
Similarly, an electron donating groups (–OCH3) in an alcohol (Table 4; entry 7) reduced the
reactivity of the alcohol substrate for oxidative-dehydrogenation giving less conversion
(50%). Due to long range effectiveness of inductive effect,27 the electron donating group can
strengthen alcoholic O–H bond reducing the acidity of alcohol and slowing down
deprotonation and benzylic H- elimination. Therefore, longer reaction period (48 h) increased
the conversion of alcohol (90%; Table 4; entry 7). The higher acidity of alcohol due to an
electron-withdrawing group (–NO2) was helpful for oxidative-dehydrogenation giving 95%
conversion in 24 h (Table 4; entry 8).
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
The nature of a substituent present in amines can affect the nucleophilicity of amine
substrates, which can affect the reaction rate (conversion) and the selectivity of cross-imine.
The presence of an electron withdrawing group (–NO2) in an amine will reduce its
nucleophilicity and therefore, reactivity for trans-imination reaction giving less selectivity to
cross-imine (Table 4; entry 5). However, the poor nucleophilicity of amine (having an
electron withdrawing group) did not show such effect in the reaction with alcohol (Table 4;
entry 10). This may be due to good reactivity of carbonyl intermediate (i.e., benzaldehyde)
for reaction with aniline derivatives. This was confirmed by carrying out reactions of
benzaldehyde (10 mmol) with all the derivatives of aniline (10 mmol) at 180°C without using
a catalyst, which gave complete conversion of benzaldehyde within 4 h with 100% selectivity
of cross-imine.
The oxidative-dehydrogenation activity of AHT-3 was also demonstrated for some tandem
reactions to use alcohols as reagent. The reactions shown in Table 5 are conventionally
carried out by base catalyzed reactions using an aldehyde (benzaldehyde).28 The tandem
reactions using 1b as reactant have been reported with noble/ transition metal based catalysts,
which involves conversion of 1b into benzaldehyde followed by base catalyzed condensation
with a substrate.1a-e The AHT-3 showed good activity in these reactions giving substantial
20

Page 21 of 26
New Journal of Chemistry
View Article Online
DOI: 10.1039/C9NJ06096K
1
2
3
4
5
6
7
8
9
conversion of 1b and selectivity of desired products. The by-products of reactions (Table 5;
entry 1 and 2) are convertible into the desired product.28c,29 The conversion and selectivity of
the desired products in these reactions can be further improved by optimizing the reaction
conditions (temperature, reaction time, molar ratio of reactants, catalyst amount, etc.).
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Table 5. Conversion of 1b in AHT-3 catalyzed C–C bond forming tandem reactions.
Selectivity (%)
Entry
1b
Substrate
Conv. (%) of 1b
Desired
product
By-product
O
OH
O
O
O
1
51
54
46
O
O
OH
OH
O
2
3
89
87
57
9a
-
CN
NC CN
C
CN
H
2
100
aOther by-product: cyclohexanone.
4. Conclusions
The Mg-Al mixed oxide (Mg/Al ratio = 3.0) was found to be an efficient and inexpensive
catalyst (precious metal free) for imination reactions to synthesize cross-imines with high
selectivity and for tandem reactions utilizing alcohols as reagent. The nature of substituent
present in benzylic substrates and coupling amines influences the conversion rate and
selectivity of cross-imines in imination reactions. The alcohols are better substrates than
amine substrates for selective synthesis of cross-imines. The surface basic sites of catalyst
catalyze imination and tandem reactions by activating benzylic substrates for oxidative-
dehydrogenation. This study may further explore the wide application of Mg-Al HTs and
mixed oxides as catalyst to activate alcohols via oxidative-dehydrogenation for tandem
reactions.
21

New Journal of Chemistry
Page 22 of 26
View Article Online
DOI: 10.1039/C9NJ06096K
1
2
3
Conflicts of Interest
4
5
6
There are no conflicts of interests to declare by the authors.
7
8
9
Acknowledgments
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Authors are thankful to Dr. H.M. Desai, Vice-Chancellor, DDU for providing necessary
facilities and encouragement and University Grant Commission (UGC), New Delhi, India for
providing financial support (F. No.-43-215/2014 SR) under Major Research Project scheme.
References
1
(a) W. Zhou, S. Zhai, J. Pan, A. Cui, J. Qian, M. He, Z. Xu, and Q. Chen, Asian J. Org.
Chem., 2017, 6, 1536–1541; (b) Y. A. Li, S. Yang, Q. K. Liu, G. J. Chen, J. P. Ma and Y.
B. Dong, Chem. Commun., 2016, 52, 6517–6520; (c) L. Xu, C. G. Li, K. Zhang and P.
Wu, ACS Catal., 2014, 4, 2959–2968; (d) K. Liu, Y.Q. Xu, Z.X. Yao, H.N. Miras and
Y.F. Song, ChemCatChem 2016, 8, 929–937; (e) C. Chen, H.M. Yang, J.Z. Chen, R.
Zhang, L. Guo, H.M. Gan, B.N. Song, W.W. Zhu, L. Hua and Z.S. Hou, Catal. Commun.,
2014, 47, 49–53.
2
(a) J. Bain, P. Cho and A. Voutchkova-Kostal, Green Chem., 2015, 17, 2271–2280; (b) B.
Chen, J. Li, W. Dai, L. Wang and S. Gao, Green Chem., 2014, 16, 3328–3334; (c) H.
Sun, F.Z. Su, J. Ni, Y. Cao, H.-Y. He and K.N. Fan, Angew. Chem. Int. Ed., 2009, 48,
4390–4393; (d) M. Tamura and K. Tomishige, Angew. Chem. Int. Ed., 2015, 54, 864–
867; (e) S. Sithambaram, R. Kumar, Y.-C. Son and S.L. Suib, J. Catal., 2008, 253, 269–
277; (f) W. He, L. Wang, C. Sun, K. Wu, S. He, J. Chen, P. Wu and Z. Yu, Chem. Eur. J.,
2011, 17, 13308–13317; (g) H. Wang, J. Zhang, Y.-M. Cui, K.-F. Yang, Z.-J. Zhenga and
L.-W. Xu, RSC Adv., 2014, 4, 34681–34686; (h) G. Jaiswal, V.G. Landge, D. Jagadeesan
22

Page 23 of 26
New Journal of Chemistry
View Article Online
DOI: 10.1039/C9NJ06096K
1
2
3
4
5
and E. Balaraman, Green Chem., 2016, 18, 3232-3238; (i) R. Tomar, K. Ebitani and R.
Chandra, ChemistrySelect 2019, 4, 3577 –3581.
6
7
8
9
3
(a) M. Gopiraman, K. Wei, K.-Q. Zhang, I.-M. Chung and I.S. Kim, RSC Adv.,2018,
8,4531–4547; (b) D. Ge, G. Qu, X. Li, K. Geng, X. Cao and H. Gu, New J
Chem., 2016, 40, 5531–5536; (c) X. Qiu, C. Len, R. Luque and Y. Li, ChemSusChem,
2014, 7, 1684–1688; (d) R.D. Patil and S. Adimurthy, Adv. Synth. Catal., 2011, 353,
1695–1700; (e) D. Dissanayake, L.A. Achola, P. Kerns, D. Rathnayake, J. He, J.
Macharia and S.L. Suib, Appl. Catal. B: Environ., 2019, 249, 32–41; (f) C. Ge, X. Sang,
W. Yao, L. Zhang and D. Wang, Green Chem., 2018, 20, 1805–1812.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
4
(a) Jin Li, Yang Xu, Shuai Wang, and Hui Zhang, J. Phys. Chem. 123 (2019) 15483–
15494; (b) S. Nishimura, Y. Yakita, M. Katayama, K. Higashimine and K. Ebitani, Catal.
Sci. Technol., 2013, 3, 351–359; (c) W.H. Fang, J.S. Chen, Q.H. Zhang, W.P. Deng, Y.
Wang, Chem. Eur. J. 2011, 17, 1247–1256; (d) H. Tsunoyama, N. Ichikuni, H. Sakurai,
T. Tsukuda, J. Am. Chem. Soc. 2009, 131, 7086–7093.
5
S.I. Murahashi and Y. Imada, in: M. Beller and C. Bolm (Eds.), Wiley–VCH, Weinheim,
Germany, 2004, pp. 497–505.
6
7
B. Chen, L and Wang, S. Gao, ACS Catal., 2015, 5, 5851–5876.
(a) J. Chen, J. Cen, X. Xu and X. Li, Catal. Sci. Technol., 2016, 6, 349–362; (b) X. Lang,
X. Chen and J. Zhao, Chem. Soc. Rev., 2014, 43, 473–486; (c) S.-I. Naya, K. Kimura and
H. Tada, ACS Cata., 2013, 3, 10−13; (d) N. Li, X. Lang, W. Ma, H. Ji, C. Chen and J.
Zhao, Chem. Commun., 2013, 49, 5034−5036; (e) X. Lang, W. Ma, Y. Zhao, C. Chen, H.
Ji and J. Zhao, Chem. Eur. J., 2012, 18, 2624−2631.
8
(a) A. Monopoli, P. Cotugno, F. Iannone, F. Ciminale, M.M. Dell’Anna, P. Mastrorilli
and A. Nacci, Eur. J. Org. Chem., 2014, 27, 5925–5931; (b) H. Huang, J. Huang, Y.-M.
23

New Journal of Chemistry
Page 24 of 26
View Article Online
DOI: 10.1039/C9NJ06096K
1
2
3
4
5
6
7
8
Liu, H.-Y. He, Y. Kao and K.-N. Fan, Green Chem., 2012, 14, 930–934; (c) L. Liu, S.
Zhang, X. Fu and C.-H. Yan, Chem. Commun., 2011, 47, 10148–10150.
K.N. Tayade and M. Mishra, J. Mol. Catal. A: Chem., 2014, 382, 114–125.
9
9
10 S.M. Landge, V. Atanassova, M. Thimmaiah and B. Torok, Tetrahedron Lett., 2007, 48,
5161–5164.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
11 (a) R. Reddy Donthiri, R.D. Patil and S. Adimurthy, Eur. J. Org. Chem., 2012, 4457–
4460; (b) J. Xu, R. Zhuang, L. Bao, G. Tang and Y. Zhao, Green Chem., 2012, 14, 2384–
2387.
12 S. Kobayashi, Y. Mori, J.S. Fossey and M.M. Salter, Chem. Rev., 2011, 111, 2626–2704.
13 A. Vaccari, Catal. Today, 1998, 41, 53–71.
14 (a) A. Corma, V. Fornes and F. Rey, J. Catal.,1994, 148, 205–212; (b) J.L.I. Di Cosimo,
G. Torres and C.R. Apesteguia, J. Catal., 2002, 208, 114–123; (c) C. Carlini, M.
Marchionna, M. Noviello, A.M. Raspolli Galletti, G. Sbrana, F. Basile and A. Vaccari, J.
Mol. Catal. A: Chem., 2005, 232, 13–20.
15 M. Dixit, M. Mishra, P.A. Joshi and D.O. Shah, J. Ind. Eng. Chem., 2013, 19, 458–468.
16 J.C.A.A. Roelofs, J.A. van Bokhoven, A.J. van Dillen, J.W. Geus and K.P. de Jong,
Chem. Eur. J., 2002, 8, 5571-5579.
17 S.K. Sharma, P.A. Parikh and R.V. Jasra, Appl. Catal. A: Gen., 2010, 386, 34–42.
18 V. Rives and S. Kannan, J. Mater. Chem., 2000, 10, 489-495.
19 J.I. Di Cosimo,V.K. Diez, M. Xu, E. Iglesia and C.R. Apesteguia, J. Catal.,1998, 178,
499–510.
20 V.K. Diez, C.R. Apesteguia and J.I. Di Cosimo, J. Catal., 2003, 215, 220–233.
21 A. Grirrane, A. Corma and H. Garcia, J. Catal., 2009, 264, 138–144.
22 B. Tyagi, M.K. Mishra, R.V. Jasra, J. Mol. Catal. A: Chem., 2007, 276, 47–56.
23 K.N. Tayade and M. Mishra, Catal. Sci. Technol., 2013, 3, 1288–1300.
24

Page 25 of 26
New Journal of Chemistry
View Article Online
DOI: 10.1039/C9NJ06096K
1
2
3
4
5
6
7
8
24 B. Granqvist, T. Sandberg and M. Hotokka, J. Colloid Interface Sci., 2007, 310, 369–376.
25 A.J. GeUman and Q. Dai, J. Am. Chem. Soc., 1993, 115, 114–722.
26 X. Wang and D.Z. Wang, Tetrahedron, 2011, 67, 3406–3411.
9
27 R. Tandon, T.A. Nigst, H. Zipse, Eur. J. Org. Chem., 2013, 24, 5423–5430.
28 (a) M. Climent, A. Corma, S. Iborra, A. Velty, J. Catal., 2004, 221(2), 474–482; (b) J.J.
Shrikhande, M.B. Gawande, R.V. Jayaram, Catal. Commun., 2008, 9, 1010–1016; (c) M.
Vashishtha, M. Mishra, S. Undre, M. Singh, D.O. Shah, J. Mol. Catal. A: Chem., 2015,
396, 143–154.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
29 A. Charvieux, J.B. Giorgi, N. Duguet, E. Métay, Green Chem., 2018, 20, 4210–4216.
25

New Journal of Chemistry
Page 26 of 26
View Article Online
DOI: 10.1039/C9NJ06096K
1
2
3
4
Graphical Abstract
5
6
7
8
Catalytic activity of Mg-Al hydrotalcites and derived mixed oxides for imination reactions
via oxidative-dehydrogenation mechanism
9
Naresh Vala,a Pradyuman A. Joshi,a Manish Kumar Mishra b,*
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
aDepartment of Chemical Engineering, Faculty of Technology, & Shah-Schulman Center for Surface Science and
Nanotechnology, Dharmsinh Desai University, College Road, Nadiad 387 001, Gujarat, India
bDepartment of Chemistry, Sardar Patel University, Vallabh Vidyanagar 388 120, Gujarat, India
Abstract
Mg-Al hydrotalcite derived mixed oxide (Mg/Al ratio = 3.0) showed excellent catalytic activity
in imination and tandem reactions via oxidative-dehydrogenation mechanism.
-
Ph
Ph
Ph
H
Ph
CH
Nu
CH2
CH
X
CH
Nu
O2
-H2O2
Adsorption
XH
Benzylic
substrate
X
+
H
Nu = Nucleophile
M
(amine/ carbanion)
g
X = NH or O
B
-
A
l
m
i
x
(
M
e
d
g
/
B
o
)
A
x
l
=
i
=
d
b
e
3
a
s
i
c
s
i
t
e
* Inexpensive, noble/ transition metal free catalyst,
* Solvent-, base- and oxidant- free condition,
* Selective synthesis of cross-imines,
* Use of alcohols as greener reagents.