Tandem catalysis: Direct catalytic synthesis of imines from alcohols using manganese octahedral molecular sieves

Article abstract of DOI:10.1016/j.jcat.2007.11.006

Tandem processes involving catalysts can offer unique and powerful strategies for converting simple starting materials into more complex products in a single reaction vessel. Imines were synthesized directly from alcohols via a tandem catalytic process using manganese octahedral molecular sieves (OMS-2) as catalyst. The synthesis proceeds through two steps: an oxidation of the alcohols to carbonyls followed by the nucleophilic attack by an amine on the carbonyl to form the imine. OMS-2 acts as a bifunctional catalyst and catalyzes two mechanistically distinct processes in a single reaction vessel under the same conditions. Conversions up to 100% were obtained for benzylic alcohols with this efficient, environmentally friendly catalytic reaction. The advantages of this process are that the intermediates need not be isolated and the catalysts can be reused upon simple filtration without loss of activity.

Full text of DOI:10.1016/j.jcat.2007.11.006

Journal of Catalysis 253 (2008) 269–277
www.elsevier.com/locate/jcat
Tandem catalysis: Direct catalytic synthesis of imines from alcohols
using manganese octahedral molecular sieves
Shanthakumar Sithambaram b, Ranjit Kumar b, Young-Chan Son b, Steven L. Suib a,∗
a
Department of Chemistry, Department of Chemical Engineering, and Institute of Materials Science, University of Connecticut, U-3060,
55 North Eagleville Rd., Storrs, CT 06269-3060, USA
b
Department of Chemistry, University of Connecticut, U-3060, 55 North Eagleville Rd., Storrs, CT 06269-3060, USA
Received 12 August 2007; revised 2 November 2007; accepted 7 November 2007
Abstract
Tandem processes involving catalysts can offer unique and powerful strategies for converting simple starting materials into more complex
products in a single reaction vessel. Imines were synthesized directly from alcohols via a tandem catalytic process using manganese octahedral
molecular sieves (OMS-2) as catalyst. The synthesis proceeds through two steps: an oxidation of the alcohols to carbonyls followed by the
nucleophilic attack by an amine on the carbonyl to form the imine. OMS-2 acts as a bifunctional catalyst and catalyzes two mechanistically
distinct processes in a single reaction vessel under the same conditions. Conversions up to 100% were obtained for benzylic alcohols with this
efficient, environmentally friendly catalytic reaction. The advantages of this process are that the intermediates need not be isolated and the catalysts
can be reused upon simple filtration without loss of activity.
© 2007 Elsevier Inc. All rights reserved.
Keywords: Heterogeneous catalysis; Imines; Manganese octahedral molecular sieves
1. Introduction
palladium/amberlyst catalysts have been used to carry out de-
hydration of the tertiary alcohol and the hydrogenation of the
in situ formed alkene in a single vessel [4]. In another ex-
ample, caprolactam, a precursor for Nylon-6, which generally
requires a two step synthesis, was synthesized in high yields
in a single-pot using an aluminophosphate bifunctional hetero-
geneous catalyst [5]. The finding and utilization of a single
catalyst to promote more than one transformation in a selective
manner is a promising area of research [6]. Such direct syn-
thesis routes help to avoid side product formation and loss of
starting material as well as to reduce capital investment and op-
eration costs.
Imines are very versatile intermediates in synthetic organic
chemistry and pharmaceutical compounds such as β-lactams
[6–8]. Imines have potential for therapeutic applications such
as anti-inflammatory agents and anti-cancer agents [9,10]. Sev-
eral methods for the synthesis of imines are described in
the literature; they can be obtained from aldehydes [11], pal-
ladium catalyzed amination [12], formamides [13], and by
polymer-supported [14]. However, these methodologies often
require complex procedures and long reaction times. A tan-
Tandem processes that involve multiple chemical transfor-
mations in a single-pot with minimal work up and less waste
generation have revolutionized synthetic chemistry in recent
years [1]. Tandem catalytic processes can replace multi-step
syntheses with efficient catalytic reactions that can have sig-
nificant impact on the manufacture of fine chemicals and phar-
maceutical intermediates [2]. These processes are very efficient
in terms of work up and catalyst utilization, and provide the
advantage that intermediates do not require isolation where
they are unstable or difficult to handle (e.g., toxic, volatile
or prone to polymerize). When a reaction that involve two or
more mechanistically distinct processes promoted by a sin-
gle catalyst, the process is called auto tandem catalysis [3].
Recently, there have been many reports of heterogeneous bi-
functional catalysts used for single-pot synthesis. Bifunctional
*
Corresponding author. Fax: +1 860 486 2981.
E-mail address: steven.suib@uconn.edu (S.L. Suib).
0021-9517/$ – see front matter © 2007 Elsevier Inc. All rights reserved.
doi:10.1016/j.jcat.2007.11.006

270
S. Sithambaram et al. / Journal of Catalysis 253 (2008) 269–277
nitric acid (6.8 mL) to a 500 mL of round bottom flask with a
condenser. The dark brown slurry was refluxed for 24 h, then
filtered and washed with deionized water several times. The
catalyst was dried at 120 ◦C overnight before use. H+ sub-
stituted K-OMS-2 was obtained by ion-exchanging K-OMS-2
with HNO3. K-OMS-2 was stirred in 1 M solution of nitric acid
for 6 h between 60–70 ◦C to prepare H-K-OMS-2.
Fig. 1. Structure of OMS-2 catalysts.
2.3. X-Ray powder diffraction studies
dem oxidation-imine formation process with active manganese
oxide to produce imines directly from alcohols has been re-
ported [15], but the method has a serious drawback that it
requires an excess amount of active manganese oxide as the sto-
ichiometric oxidant and 4 Å molecular sieves as the dehydrating
agent. Furthermore, the reactions were done with chlorinated
solvents requiring longer reaction times.
The structure of the materials was studied by X-ray diffrac-
tion (XRD) experiments. A Scintag 2000 PDS instrument with
CuKα radiation with a beam voltage of 45 kV and a beam cur-
rent of 40 mA was used to collect the X-ray data. The X-ray
patterns of the catalysts were compared to that of the standard
OMS-2 materials (JCPDS file # 29-1020) (Fig. 2).
Catalytic applications of octahedral molecular sieves (OMS)
of manganese oxides are well known and the recent examples
have been efficient oxidation of alcohols [16] and epoxida-
tion of olefins [17]. In comparison, active manganese oxide
requires 5–10 equivalents of oxidant for alcohol oxidation reac-
tions [18], where as only ∼0.5 equivalent of OMS-2 is needed.
Environmentally friendly catalytic reactions have tremendous
advantages over those that use a stoichiometric reagent. Various
types of OMS have been synthesized in our laboratory and the
characterization and applications are well established [19,20].
For the present study, OMS-2 (cryptomelane) type materials
were used as catalysts. OMS-2 consists of a one-dimensional
tunnel structure formed by 2 × 2 edge shared MnO6 octahe-
dra (Fig. 1). The composition of K-OMS-2 is KMn8O16·nH2O
and the tunnels have dimensions of 4.6 × 4.6 Å. The aver-
age oxidation state of Mn in K-OMS-2 is ∼3.8 containing of
Mn4+, Mn3+, and Mn2+ ions in the framework. The surface
area is ∼90 m2/g, mesopore and total pore volumes are 0.29
and 0.49 cm3/g, respectively [21,22,39].
2.4. Scanning electron microscopy
Scanning Electron Micrographs were taken on a Zeiss DSM
982 Gemini field emission scanning microscope with a Schot-
tky Emitter at an accelerating voltage of 2 kV with a beam
current of 1 µA. The images showed a characteristic fibrous
morphology of OMS-2 materials (Fig. 3).
2.5. Reaction procedure
Alcohol (1 mmol), toluene (10 mL), primary amine (2–
5 mmol), and K-OMS-2 (50 mg) were added to a 50 mL round-
bottomed flask. The mixture was stirred under reflux for 12–
24 h at 110 ◦C in air and the reaction progress was monitored
by TLC. After the reaction, the mixture was cooled, OMS-2
was removed by filtration, and the products were analyzed.
2.6. Analytical procedure
In this paper we report a more efficient tandem catalytic
process to form imines directly from alcohols using OMS-2 as
a catalyst. OMS-2 acts as a bifunctional catalyst in this reac-
tion to oxidize the alcohols to the carbonyls and subsequently,
acts as a Lewis acid to form imines. These two mechanistically
distinct steps are catalyzed by OMS-2 in a single reaction ves-
sel under the same conditions. The process does not require any
additives for water removal.
Gas chromatography-mass spectroscopy (GC-MS) method
was used for the identification and quantification of the prod-
uct mixtures. GC-MS analyses were done using an HP 5890
series II chromatograph with a thermal conductivity detector
coupled with an HP 5970 mass selective detector. An HP-1
column (non polar cross linked siloxane) with dimensions of
12.5 m × 0.2 mm × 0.33 µm was used in the gas chromato-
graph. 1H and 13C NMR were collected on a Brucker DRX-400
(400.144 MHz 1H, 100.65 MHz 13C).
2. Experimental
3. Results
2.1. Reagents
3.1. Effect of alcohols and amines
All chemicals were purchased from Aldrich and were used
without further purification unless noted otherwise.
The initial imine synthesis was carried out using benzyl al-
cohol with butyl amine in toluene under reflux (110 ◦C) in the
presence of air. A 100% conversion and 99% selectivity for the
corresponding imine were obtained in 12 h. The optimum con-
ditions were then extended to a range of other benzyl, allyl and
alkyl alcohols with primary amines as exemplary reactions. Ta-
ble 1 shows the results of the effects of various alcohols on
2.2. Catalyst synthesis
K-OMS-2 was prepared and characterized using a procedure
reported in the literature [19]. Potassium permanganate solu-
tion (0.4 M, 225 mL) was added to a mixture of manganese
sulfate hydrate solution (1.75 M, 67.5 mL) and concentrated

S. Sithambaram et al. / Journal of Catalysis 253 (2008) 269–277
271
Fig. 2. XRD patterns of K-OMS-2 and H-K-OMS-2 catalysts.
Fig. 3. FESEM images of K-OMS-2 and H-K-OMS-2 catalysts.
the conversion and selectivity for imines. The conversion was
100% in the case of benzylic alcohols, whereas the selectivity
towards imine was about 99% in most cases (entries 1 and 2).
Reactions were faster when butyl amine was reacted with al-
cohols as compared to the case where aniline was reacted with
the alcohols. When the reactions were done with aniline as the
base it took 24 h for the reaction to be completed. 2-thiophene
methanol (entry 3) and cinnamyl alcohol (entry 4) gave lower
conversions when reacted with aniline as compared to when
they were reacted with butyl amine. Aliphatic primary and sec-
ondary alcohols gave low conversions, however the selectivity
for imine was still 100% (entries 5 and 7).
The effect of various substituents on the benzene ring was
evaluated in the imine synthesis and the results are listed in
Table 2. 4-methoxy benzyl alcohol with aniline (entry 8) gave
77% conversion 71% selectivity for imine. 4-Methyl benzyl al-
cohol (entry 9) gave 89% conversion and 90% selectivity for
the corresponding imine. In contrast, 4-nitro benzyl alcohol
and 4-chloro benzyl alcohol (entries 10 and 11) showed 100%
conversions and 100 and 99% selectivities, respectively. When
the aniline was changed to p-nitro aniline and reacted with
4-methoxy benzyl alcohol the conversion was only 66% and
selectivity was 39% (entry 12).
In order to determine the role of OMS-2 in the formation
of the imine in the second step, a series of reactions were
done starting from aldehydes and amines with and without the
catalyst (Table 3). The conversions were higher when the cat-
alyst was used than without in all cases (entries 13–15). The
reaction between p-methoxybenzaldehyde and p-nitroaniline
in presence of the catalyst afforded 81% imine, and the reac-
tion without the catalyst gave only 21% imine. Similar trend in
results were observed for the other two reactions with 3,4-di-
methoxybenzaldehyde and 4-methylbenzaldehyde as substra-
tes.

272
S. Sithambaram et al. / Journal of Catalysis 253 (2008) 269–277
Table 1
Synthesis of imines from alcohols and amines
a
b
c
d,e
Entry
1
Substrate
Product
Amine
Conversion
Selectivity
Bu-NH
100
100
100
99
100
99
2
2
Ph-NH
2
2
Bu-NH
Ph-NH
100
97
99
99
97
2
3
4
Bu-NH
2
Ph-NH
75
2
f
c
f
Bu-NH
Ph-NH
99(99)
80 (100)
2
f
f
58(61)
74(84)
2
5
6
Bu-NH
Bu-NH
Bu-NH
44
25
100
2
2
2
100
100
7
a
12
◦
Reaction conditions: 1 mmol alcohol, 2 mmol amine, 10 mL toluene as solvent, 50 mg of K-OMS-2 as catalyst, reflux at 110 C, t = 12 h for butylamine, 24 h
for aniline.
b
c
d
e
f
Bu-NH = n-butylamine, Ph-NH = aniline.
2
2
−1
Conversion (%) based on substrate = [1− ((concentration of substrate left after reaction) × (initial concentration of substrate) )] ×100.
Selectivity for imines, other product was aldehyde.
−1
Selectivity (%) of product = ((concentration of product) × (total concentration of all products) ) ×100.
Catalyst was H-K-OMS-2.
Shape selectivity of the substrate was studied by reacting
solvent, gave 99% conversion and 100% selectivity (entry 20).
various benzene dimethanols with butylamine and the results
are shown in Table 4. Imine formation with benzene dimethanol
and butyl amine gave interesting results. Among the benzene
dimethanol substrates (entries 16–18), benzene-1,4-dimethanol
gave the highest selectivity (100%) for its diimine. Benzene-
1,3-dimethanol gave 100% conversion, but the selectivity of the
diimine was only 20% and the rest was the monoimine. There
was no dimine formed when benzene-1,2-dimethanol was re-
acted with butylamine. However, in addition to monoimines,
the formation of 3H-benzofuran-2-one was observed. Ben-
zoin, a hydroxyl ketone was also reacted with butylamine, and
showed 24% selectivity for dimine and 76% selectivity for the
monoimine.
Xylene (entry 21) showed 85% conversion and very selective
imine formation. The other non-polar solvent, octane (entry 22)
gave only 50% conversion and resulted in the formation of a
mixture of benzaldehyde and imine, showing partial selectivity
to imine. Polar solvent such as acetonitrile (entry 23) gave only
34% conversion.
3.3. Catalyst reusability and stability
The reusability of the catalyst was tested with “spent” K-
OMS-2. The catalyst was recovered by filtration after the re-
action, regenerated by washing with acetone and water and
then drying at 300 ◦C for 6 h. The regenerated catalyst was
reused four times without any appreciable loss of activity.
XRD pattern of K-OMS-2 before and after the reaction indi-
cates that the structure of K-OMS-2 is retained after the reac-
tion.
3.2. Effect of solvents
Effect of various polar and non-polar solvents was investi-
gated for the reaction of benzyl alcohol with butyl amine to
form the corresponding imine as shown in Table 5. Toluene was
found to be the best solvent for this reaction under the condi-
tions used for this reaction. Toluene, a non-polar and aprotic
To rule out any possibility of homogeneous catalysis, we ran
the reaction between p-anisyl alcohol and aniline (entry 8) for
12 h (conversion 54%). Then the catalyst was removed by fil-

S. Sithambaram et al. / Journal of Catalysis 253 (2008) 269–277
273
Table 2
The effect of electron donating and electron withdrawing groups
a
Entry
Substrate
Amine
Product
Conversion
77
Selectivity
b
8
71
b
9
10
11
89
100
100
90
100
99
b
12
a
66
39
◦
Reaction conditions: 1 mmol alcohol, 2 mmol amine, 10 mL toluene as solvent, 50 mg of K-OMS-2 as catalyst, reflux at 110 C, t = 24 h.
b
The other product was aldehyde.
Table 3
Effect of catalyst on imine synthesis from aldehydes
a
Entry
13
Substrate
Product
OMS-2
86
No OMS-2
77
14
81
74
21
16
15
a
◦
Reaction conditions: 1 mmol aldehyde, 2 mmol 4-nitroaniline, 10 mL toluene as solvent, 50 mg of K-OMS-2 as catalyst, reflux at 110 C, t = 24 h.
tration and the mixture was allowed to react for an additional
24 h. However, no change in conversion was observed. These
findings suggested that no leaching of the catalyst is occurring
under our reaction conditions.

274
S. Sithambaram et al. / Journal of Catalysis 253 (2008) 269–277
Table 4
a
Diimine formation from benzylic alcohols and amines
Entry
Alcohol
Product (selectivity, %)
16
b
(78%)
(3%)
17
18
(80%)
(20%)
(100%)
19
a
(76%)
(24%)
◦
Reaction conditions: 1 mmol alcohol, 5 mmol butylamine, 10 mL toluene as solvent, 50 mg of K-OMS-2 as catalyst, reflux at 110 C, t = 24 h. Conversion is
100% in all cases. Amine: n-butyl amine, Bu: CH CH CH CH –.
b
3
2
2
2
Other product was 3H-benzofuran-2-one.
Table 5
this stoichiometric protocol is the generation of large amounts
of heavy metal waste. Another disadvantage of stoichiometric
oxidant is that, over oxidation can lead to the formation of unde-
sirable side products. This gives rise to the need for milder cat-
alytic processes utilizing dioxygen or peroxides as the oxygen
source. Due to the handling hazards associated with peroxides,
molecular oxygen is preferred as an environmentally accept-
able, selective, and strong oxidant for liquid-phase oxidations
[24]. Pd, Pt and Ru based catalysts have been widely used for
oxidation in the presence of molecular oxygen in supercritical
fluids [25]. Au based catalysts have demonstrated very interest-
ing and promising activity in oxidation [26]. Even though these
processes use small amounts of catalysts, they yield low con-
versions or several products due to over oxidation.
a
The effect of solvents on imine formation
Entry
Solvent
Reaction tem-
Conversion
(%)
Selectivity
(%)
◦
perature ( C)
b
20
21
22
Toluene
Xylene
Octane
110
145
125
99
85
50
100
100
b
b
78
c
22
b
23
Acetonitrile
80
34
57
c
27
d
16
a
Reaction conditions: 1 mmol benzylalcohol, 2 mmol butylamine, 10 mL
solvent, 50 mg of K-OMS-2 as catalyst, reflux, t = 12 h.
b
Imine (N-benzyl butylamine).
Aldehyde (benzaldehyde).
Ester (benzyl benzoate).
c
d
Imine formation from carbonyls and amines in general, is
a facile reaction due to the good electrophilic properties of
carbonyls and nucleophilic properties of amines, and may not
require a catalyst. However, in the presence of factors that de-
crease electrophilicity/nucleophilicity of the carbonyl/amine,
a catalyst may be required for the transformation. Transition
metal based catalysts have been extensively used for the imine
formation from aldehydes or ketones. Some examples include
ZnCl2, TiCl4, alumina, and CuSO4 that act as Lewis acids to
catalyze a nucleophilic attack on the carbonyl group by the
amine as well as serving as dehydrating agents [27–30]. Imines
have been synthesized under microwave irradiation using clays
as catalysts [31]. More recently, ultrasound irradiation coupled
with silica catalysts have been utilized to synthesize imines
4. Discussion
4.1. Catalytic activity
The imine synthesis from alcohols involves two steps. The
first step involves the oxidation of the alcohol to its correspond-
ing carbonyl compound, an aldehyde in the case of a primary
alcohol or a ketone in the case of a secondary alcohol. The car-
bonyl compound then reacts with an amine to form the imine in
the second step. Alcohol oxidation to form carbonyls is tradi-
tionally performed with stoichiometric amounts of Cr(VI) com-
pounds or other inorganic oxidants [23]. The major drawback of

S. Sithambaram et al. / Journal of Catalysis 253 (2008) 269–277
275
Table 6
Butylamine which is more basic as compared to aniline helps in
providing an environment which helps in the proton abstraction
step in the oxidation of alcohols (Scheme 2). The lower basic-
ity of aniline also results in a lower rate of nucleophilic attack
by the amine on the carbonyl carbon to form imines; therefore
it takes more time for the formation of imines in the case of
aniline as compared to butyl amine.
Comparison of activity between K-OMS-2 and active MnO
2
a
Catalyst
Reaction
time (h)
Yield
(%)
TON
16
TOF
(h
−1 b
)
c
The effect of substituents in the substrates was very promi-
nent in conversions and selectivities for imine synthesis (Ta-
ble 2). The presence of electron donating groups, –OCH3
and –CH3 at the para position of the alcohol resulted in lower
conversion and selectivity for imines. In contrast, electron with-
drawing groups in the para position of the alcohol afforded
enhanced conversion and selectivity for imines. Electron do-
nating groups electron density in the benzene rings of the al-
cohol and this result in the difficulty in oxidation process and
reduced electrophilicity of in situ formed carbonyl. Electron
withdrawing groups in the alcohols can enhance oxidation and
electrophilicity. This effect is reversed in the aniline leading to
either an increase or a decrease in nucleophility depending on
the groups present in the ring. These effects were prominent
in the reaction between 4-methoxy benzyl alcohol and 4-nitro
aniline where the decrease in conversion is due to lower ba-
sicity of p-nitroaniline as compared to aniline, as has been
the case, which was discussed earlier. The presence of elec-
tron withdrawing nitro group at the para position in aniline also
decreases the nucleophilicity of the amine, therefore the selec-
tivity for the imine is also lower.
Among the benzene dimethanol substrates (Table 4, en-
tries 16–18), para-dimethanol gave a higher conversion to di-
imine than the ortho- or meta-dimethanol. These results show
that both the alcohol groups in benzene-1,4-dimethanol were
easily accessible to the active centers in K-OMS-2, whereas
in the case of ortho and meta-dimethanol, one of the alcohol
reacted first and formed the imine and subsequently the other
alcohol group got oxidized and reacted with the amine to form
the imine. Benzene-1,4-dimethanol which has a smaller kinetic
diameter as compared to 1,2- and 1,3-dimethanol, gives higher
selectivity for the corresponding di-imine; this may be due to
the way the dimethanols are oriented inside the tunnel, and their
accessibility to the active manganese centers.
K-OMS-2
Active MnO
a
12
24
100
95
1.3
0.0040
d
0.096
2
Turnover number (TON) = (moles of converted substrate) × (moles of
−1
catalyst)
.
b
Turnover frequency (TOF) = (moles of converted substrate) × ((moles of
−1
catalyst) × (reaction time in h))
.
c
50 mg K-OMS-2 = 0.0625 mmol.
d
Calculation based on data in Ref. [33].
from a range of aldehydes [32]. However, the catalysts men-
tioned above may not function as bifunctional catalysts to cat-
alyze both oxidation and imine formation in a single vessel. Ac-
tivated manganese oxides have been used in a similar process to
synthesize amines via imines from alcohols [33]. The reaction
requires 10 equivalents of activated manganese oxide in addi-
tion to 4 Å molecular sieves to accomplish the task. The role
of manganese dioxide in this case is a stoichiometric oxidant
rather than a true catalyst, and hence the recovery and reusabil-
ity are not feasible. 4 Å molecular sieves have been added to
facilitate the imine formation from in situ formed carbonyls. In
contrast, the reactions with K-OMS-2 require catalytic amount
of material and do not require any additives. In addition, higher
turnover numbers and frequencies were achieved (Table 6) with
K-OMS-2 as compared to active manganese oxide.
Benzyl, allyl and alkyl alcohols were reacted with alkyl and
aryl primary amines to form imines (Table 1). Benzylic alco-
hols gave the highest conversions and selectivities. Thiophenol,
a hetero aryl substrate showed a slightly lower conversion com-
pared to conversions obtained with benzylic alcohols. The pres-
ence of sulfur in the thiophenol substrate plays a role in the re-
tarded conversion. Allylic alcohol such as cinnamyl alcohol did
not show higher selectivity for the imine when both butylamine
and aniline were used as nucleophiles. This could be attributed
to the relatively larger size of the cinnamyl alcohol substrate.
However, when H-K-OMS-2 was used as a catalyst, the conver-
sions and selectivities were enhanced due to the higher acidity
of the H+ exchanged K-OMS-2. Aliphatic primary alcohol and
secondary alcohols gave very low conversions as compared to
primary aryl alcohols (entries 5, 6 and 7) as anticipated. The
aliphatic alcohols are difficult to oxidize to the corresponding
aldehydes and ketones with the K-OMS-2 catalyst, therefore
conversions are low. The stabilization energy of the highly con-
jugated final product obtained in entries 1–4 accounts for the
higher conversion and enhanced selectivity. When the reactions
were done with aniline it took 24 h for the reaction to be com-
pleted while when butylamine was used, it took only 12 h for
reaction completion. This shows that the nature of the amine
used in the reaction is playing a significant role in the synthe-
sis. Besides the size factors associated with the butylamine and
aniline on the nucleophic attack, their basicity plays a critical
role in the oxidation of alcohols to their aldehydes or ketones.
4.2. Solvent effects
Non-polar solvents favor the imine formation reaction ac-
cording to the results listed in Table 5. Acetonitrile, the polar
solvent, not only afforded low conversion and selectivity for
imine, but resulted in another side product benzyl benzoate.
The appearance of benzyl benzoate may be due to over oxi-
dation of the benzyl alcohol resulting in benzoic acid, which
in turn reacting with the benzyl alcohol under the conditions.
A series of control reactions was carried out to determine if any
of the products resulted due to the oxidation of the solvents.
Toluene did not give any products, but xylene afforded only
12% conversion giving both anisyl alcohol and anisaldehyde
after 60 h. However, when reaction between benzyl alcohol and
butylamine was done in xylene as the solvent for 12 h, the

276
S. Sithambaram et al. / Journal of Catalysis 253 (2008) 269–277
Scheme 1. Alcohol oxidation mechanism.
Fig. 4. Conversion of 4-methoxy benzyl alcohol (F) and selectivities of alde-
hyde (2) and imine (Q) as a function of temperature.
Scheme 2. Mechanism of imine synthesis.
oxidative products of xylene were not formed indicating that
OMS-2 selectively catalyzes the oxidation of alcohols. The ox-
idation of hydrocarbons with air using OMS-2 may require high
pressure [34].
Fig. 5. Conversion of 4-methoxy benzyl alcohol (F) and selectivities of alde-
hyde (2) and imine (Q) as a function of time.
which are difficult to synthesize due to the decrease in elec-
trophilicity/nucleophilicity of the carbonyl/amine groups (Ta-
ble 3), a catalyst such as K-OMS-2 is required.
4.3. Proposed reaction mechanism
Imine synthesis proceeds via two mechanistically distinct re-
action steps promoted by a single catalyst (K-OMS-2). The first
step involves the oxidation of the alcohol to its corresponding
ketone or aldehyde. A thorough mechanistic study of the alco-
hol oxidation with OMS-2 has been done by Makwana et al.
[35,36]. A Mars-van Krevelen-type oxidation mechanism has
been proposed. The proposed mechanism for alcohol oxidation
suggests a multi-electron redox phenomenon in the liquid phase
(Scheme 1).
The second step in imine synthesis with K-OMS-2 involves
a nucleophilic attack on the in situ generated carbonyls. Imine
formation from carbonyls is generally acid catalyzed. In situ IR
experiments following pyridine adsorption suggest that the K-
OMS-2 catalyst primarily has Lewis acidity [36]. Thus when
the amine attacks the carbonyl carbon, K-OMS-2 provides
Lewis acidic sites for oxygen in order to facilitate the cat-
alytic imine formation (Scheme 2). Imine synthesis is gener-
ally a facile reaction due to the good electrophilic properties
of carbonyls and nucleophilic properties of the amine groups,
and may not require any catalytic assistance. This was proved
when the reactions were carried out with benzaldehyde and
cinnamaldehyde as substrates. The reactions did not require
a catalyst or prolonged reaction times. However, for imines
4.4. Kinetics
Studying the reaction between 4-methoxy benzyl alcohol
and 4-nitro aniline in more detail as a function of time and tem-
perature revealed the role of K-OMS-2 in the reaction. Fig. 4
suggests that lower temperatures are unfavorable for the reac-
tion and lead to lower conversion. Higher temperatures not only
favor oxidation of the alcohol to aldehyde, but favor the con-
densation of aldehyde with the amine to form the final imine
product.
Furthermore, the studies of reaction as a function of time
(Fig. 5) show that the alcohol gets oxidized to form the alde-
hyde and then condense with the amine to form the imine.
4-methoxy benzyl alcohol is first adsorbed to the surface of
the K-OMS-2 catalyst, where an activated intermediate species
may be formed, which then is oxidized/dehydrogenated to
4-methoxy benzaldehyde. Finally, the aldehyde further reacts
with 4-nitro aniline to form the imine. Water is formed as a
by-product in both reactions. This finding is in agreement with
the proposed mechanism discussed earlier. Fig. 5 also indicates
that prolonged reaction times can enhance conversion and se-
lectivites for both aldehyde and imine.

S. Sithambaram et al. / Journal of Catalysis 253 (2008) 269–277
277
The ability to use a single catalyst, such as OMS-2 for mul-
tiple processes opens the door to higher levels of complexity
while offering advantages in terms of energy efficiency and
economy [37]. The multi-functional nature of the catalysts and
the single-pot reaction procedure can help to avoid side product
formation and can be more environmentally compatible [38].
A detailed mechanistic study of the Lewis acid catalyzed imine
formation with K-OMS-2 is underway.
[5] J.M. Thomas, R. Raja, Proc. Nat. Acad. Sci. USA 102 (2005) 13732.
[6] A. Ajamian, J.L. Gleason, Angew. Chem. Int. Ed. 43 (2004) 3754.
[7] S. Patai, The Chemistry of the Carbon–Nitrogen Double Bond (Chemistry
of Functional Goups), Wiley–Interscience, New York, 1970.
[8] J.P. Adams, J. Chem Soc. Perkin. Trans. 1 (2000) 125.
[9] D.J. Hadjipavlou-Litina, A.A. Geronikaki, Drug Des. Discov. 15 (1996)
199.
[10] M. Cushman, H.M. He, C.M. Lin, E. Hamel, J. Med. Chem. 36 (1993)
2817.
[11] A. Simion, C. Simion, T. Kanda, S. Nagashima, Y. Mitoma, T. Yamada,
K. Mimura, M. Tashiro, J. Chem. Soc. Perkin Trans. 1 (2001) 2071.
[12] J. Barluenga, F. Aznar, C. Valdes, Angew. Chem. Int. Ed. 43 (2004) 343.
[13] B.L. Feringa, J. Jensen, Synthesis (1988) 184.
[14] R. Annunziata, M. Benaglia, M. Cinquini, F. Cozzi, Eur. J. Org. Chem.
(2002) 1184.
[15] L. Blackburn, R.J.K. Taylor, Org. Lett. 3 (2001) 1637.
[16] Y.C. Son, V.D. Makwana, A.R. Howell, S.L. Suib, Angew. Chem. Int.
Ed. 40 (2001) 4280.
[17] R. Ghosh, Y.C. Son, V.D. Makwana, S.L. Suib, J. Catal. 224 (2004) 288.
[18] A.J. Fatiadi, Synthesis (1976) 65, 133.
[19] Y.F. Shen, R.P. Zerger, R.N. DeGuzman, S.L. Suib, L. McCurdy, D.I. Pot-
ter, C.L. O’Young, Science 260 (1993) 511.
[20] R.N. DeGuzman, Y.F. Shen, E.J. Neth, S.L. Suib, C.L. O’Young, S. Le-
vine, J.M. Newsam, Chem. Mater. 6 (1994) 815.
[21] S.L. Suib, Curr. Opin. Solid State Mater. Sci. 3 (1988) 63.
[22] S.L. Brock, N. Duan, Z.R. Tian, O. Giraldo, H. Zhou, S.L. Suib, Chem.
Mater. 10 (1998) 2619.
[23] T. Mallat, A. Baiker, Chem. Rev. 104 (2004) 3037.
[24] R.A. Sheldon, I.W.C.E. Arends, A. Dijksman, Catal. Today 57 (2000) 157.
[25] M. Caravati, J.-D. Grunwaldt, A. Baiker, Catal. Today 126 (2007) 27.
[26] J. Hu, L. Chen, K. Zhu, A. Suchopar, R. Richards, Catal. Today 122 (2007)
277.
5. Conclusions
In summary, an efficient tandem catalytic process to synthe-
size imines directly from alcohols using OMS-2 as a hetero-
geneous catalyst has been demonstrated. OMS-2 operating as
a bifunctional catalyst, catalyzes two mechanistically distinct
processes in a single-pot under the same reaction conditions;
namely, oxidation followed by imine-formation. Conversions
and selectivity for imines up to 100% have been achieved with-
out the need for any additives or promoters in this reaction.
This single-step catalytic imine synthesis proves to be less time-
consuming and more economical in contrast to two-step oxida-
tion of the alcohols to carbonyls and subsequent condensation
to obtain the imine. The procedure is aerobic and environmen-
tally benign. Operational simplicity and minimal waste genera-
tion of this process should be beneficial for industrial applica-
tions. The OMS-2 catalyst can be removed from the mixture by
simple filtration and can be reused.
[27] J.H. Billman, K.M. Tai, J. Org. Chem. 23 (1958) 535.
[28] F. Texier-Boullet, Synthesis (1986) 679.
[29] G. Liu, D.A. Cogan, T.D. Owens, T.P. Tang, J.A. Ellman, J. Org. Chem. 64
(1999) 1278.
Acknowledgments
We acknowledge support of the Chemical Sciences, Geo-
sciences and Biosciences Division, Office of Basic Energy Sci-
ences, Office of Science, US Department of Energy. We would
also like to thank Dr. Francis Galasso and Lin-Ping Xu for many
helpful discussions.
[30] W.B. Jennigs, C.J. Lovely, Tetrahedron Lett. 29 (1988) 3725.
[31] R.S. Varma, R. Dahiya, S. Kumar, Tetrahedron Lett. 38 (1997) 2039.
[32] K. Guzen, A.S. Guarzemini, A.T.G. Orfao, R. Cella, C.M.P. Pereira, H.A.
Stefani, Tetrahedron Lett. 48 (2007) 1845.
[33] H. Kanno, R.J.K. Taylor, Tetrahedron Lett. 43 (2002) 7337.
[34] J. Gao, X. Tong, X. Li, H. Miao, J. Xu, J. Chem. Technol. Biotechnol. 82
(2007) 620.
References
[35] V.D. Makwana, Y.C. Son, A.R. Howell, S.L. Suib, J. Catal. 210 (2002)
46.
[1] L.F. Tietz, Chem Rev. 96 (1996) 115.
[36] V.D. Makwana, L.J. Garces, J. Liu, J. Cai, Y.C. Son, S.L. Suib, Catal.
Today 85 (2003) 225.
[37] J.N. Armor, J. Appl. Catal. A 194–195 (2000) 3.
[38] W.F. Hoelderich, J. Appl. Catal. A 194–195 (2000) 487.
[39] R. Ghosh, X.-F. Shen, J.C. Villegas, Y. Ding, K. Malinger, S.L. Suib,
J. Phys. Chem. B 110 (2006) 7592.
[2] R.A. Sheldon, Pure Appl. Chem. 72 (2000) 1233.
[3] For recent review on classification of catalytic processes, see: D.E. Fogg,
E.N. dos Santos, Coord. Chem. Rev. 248 (2004) 2365.
[4] M.C. Wissler, U.-P. Jagusch, B. Sundermann, W.F. Hoelderich, Catal. To-
day 121 (2007) 6.