Solvent free acid catalysed direct N-alkylation of amines with alcohols using Al grafted MCM-41

Article abstract of DOI:10.1016/j.molcata.2014.03.010

The catalytic activity of Al grafted MCM-41 (Al-MS) was explored for solvent free acid catalysed direct N-alkylation of amines using alcohols as green alkylating agent to establish a clean method for synthesis of N-alkylated amines. The study revealed that acidity of Al-MS catalyst, reaction conditions and substrate's (amines and alcohols) nature are important factors influencing the N-alkylation reaction. The Al grafted MCM-41 with Si/Al molar ratio of 5 showed excellent activity for N-alkylation of amines with alcohols. The reusability of spent catalyst regenerated by simple washing with acetone was demonstrated for subsequent four reaction cycles.

Full text of DOI:10.1016/j.molcata.2014.03.010

Accepted Manuscript
Title: Solvent free acid catalyzed direct N-Alkylation of
amines with alcohols using Al grafted MCM-41
Author: Kamlesh N. Tayade Manish Mishra K. Munusamy
Rajesh S. Somani
PII:
S1381-1169(14)00106-X
DOI:
Reference:
http://dx.doi.org/doi:10.1016/j.molcata.2014.03.010
MOLCAA 9044
To appear in:
Journal of Molecular Catalysis A: Chemical
Received date:
Revised date:
Accepted date:
10-1-2014
15-3-2014
17-3-2014
Please cite this article as: K.N. Tayade, M. Mishra, K. Munusamy, R.S.
Somani, Solvent free acid catalyzed direct N-Alkylation of amines with alcohols
using Al grafted MCM-41, Journal of Molecular Catalysis A: Chemical (2014),
http://dx.doi.org/10.1016/j.molcata.2014.03.010
This is a PDF file of an unedited manuscript that has been accepted for publication.
As a service to our customers we are providing this early version of the manuscript.
The manuscript will undergo copyediting, typesetting, and review of the resulting proof
before it is published in its final form. Please note that during the production process
errors may be discovered which could affect the content, and all legal disclaimers that
apply to the journal pertain.

Solvent free acid catalyzed direct N-Alkylation of amines with alcohols using Al grafted
MCM-41
Kamlesh N. Tayade1, Manish Mishra1,* Munusamy K.,2 , Rajesh S. Somani2
1Department of Chemical Engineering And Shah-Schulman Center for Surface Science and Nanotechnology,
Faculty of Technology, Dharmsinh Desai University, College Road, Nadiad – 387 001, Gujarat, India.
Fax: +91 268 2520501; Tel.: +91 268 2520502; E-mail: manishorgch@gmail.com.
2Discipline of Inorganic Materials and Catalysis, Central Salt and Marine Chemicals Research Institute
(CSMCRI), Council of Scientific and Industrial Research (CSIR), GB Marg, Bhavnagar 364002, Gujarat, India.
Abstract
The catalytic activity of Al grafted MCM-41 (Al-MS) was explored for solvent free acid
catalyzed direct N-Alkylation of amines using alcohols as green alkylating agent to establish
a clean method for synthesis of N-alkylated amines. The study revealed that acidity of Al-MS
catalyst, reaction conditions and substrates (amines and alcohols) nature are important factors
influencing the N-Alkylation reaction. The Al grafted MCM-41 with Si/Al molar ratio of 5
showed excellent activity for N-Alkylation of amines with alcohols. The reusability of spent
catalyst regenerated by simple washing with acetone was demonstrated for subsequent four
reaction cycles.
Keywords: Direct N-alkylation, amines, alcohols, solid acids, Al-MCM-41.
1
Page 1 of 18

1. Introduction
The N-alkylation of amines is considered to be very important reaction in synthetic organic
chemistry [1]. The N-alkylation of amines using alcohols as alkylating agent (avoiding the
use of traditional mutagenic halide reagents) has always been preferred. In addition to
borrowing hydrogen methodology [2], the direct N-alkylation of amines using alcohols has
also been considered to be extremely atom efficient and greener process [3, 4]. The direct N-
alkylation of an amine (1) with an alcohol (2) to N-alkylated product (3) involves
nucleophilic substitution of –OH group of alcohol by –NH2 group of amine with the help of a
suitable catalyst producing water as co-product (Scheme 1).
H
Catalyst
N
+
R' OH
R NH2
R
R'
-H2O
2
3
1
Scheme 1. Direct N-alkylation of amines with alcohols.
The transition metal salts and complexes in presence of solvent, promoters and bases have
been reported as efficient homogeneous catalytic systems for direct N-alkylation of amines
with alcohols [3–7]. The transition metal (essentially noble metals) based heterogeneous
catalysts along with bases/ promoters have also been used in N-alkylation of amines with
alcohols [8–17]. However, the exploration of a ligand free, base and promoter free, and
solvent free heterogeneous catalytic system is highly desirable for direct N-alkylation of
amines. The solid acid catalysts such as nanosized zeolite beta, and proton- and metal-
exchanged montmorillonites have been studied for nucleophilic substitution reactions of a
variety of alcohols with anilines [18, 19]. The zeolites being microporous have poor reactant
diffusion efficiency and montmorillonites are thermally and chemically unstable materials.
Therefore, a robust and inexpensive acidic mesoporous material with sufficient activity for
various amine substrates would be an appropriate catalyst for N-alkylation of amines with
alcohols. Aluminium grafted mesoporous silica (Al-MCM-41) is a well explored and
2
Page 2 of 18

versatile heterogeneous acid catalyst due to its ordered structure with uniform mesopores
arranged into a hexagonal lattice, reasonably good surface area (600-1,000 m2/ gm) and high
thermal stability. The Al-MCM-41 catalysts have been studied for numerous acid catalyzed
reactions [20]. Recently we reported the potential of MCM-41 and Al-MCM-41 solid acid
catalysts for oxidative self and cross coupling of amines to imines [21]. In the present work,
the Al-MCM-41 catalyst was studied for solvent free direct N-alkylation of different amines
using alcohols to establish an efficient and greener catalytic synthesis route. The N-alkylation
reactions of amines with benzylic alcohols i.e., N-benzylation are of keen interest as it
provides access to numerous biologically active and pharmaceutically important compounds
and intermediates [22], therefore the catalytic potential of Al-MCM-41 was demonstrated for
N-alkylation of various amines with benzyl alcohol.
2. Experimental
2.1. Materials
The tetraethyl orthosilicate (TEOS; >99%), sodium hydroxide (NaOH; >97%), toluene
(99%), dichloromethane (99%) and benzyl alcohol (99%) were purchased from Merck. The
cetyl trimethylammonium bromide (CTAB; 98%), aluminium iso-propoxide (97%), p-nitro
aniline (98%), p-methoxy aniline (98%), aniline (99%), p-nitro benzyl alcohol (98%), p-
methoxy benzyl alcohol (98%), n-heptanol (99%), cyclohexanol (98%), toluene
sulphonamide (98%), benzamide (98%), acetanilide (98%), diphenyl amine (98%) and
piperazine (98%) were from s.d. Fine Chemicals, India. The benzyl amine (99%) and butane-
1,4-diol (99%) were purchased from Spectrochem. The benzene sulphonamide (98%) was
from Aldrich. All the chemicals were used without any further purification.
2.2. Synthesis and characterization of Al-MS samples
The mesoporous silica (MCM-41; MS) was synthesized by basic hydrolysis of TEOS and the
post synthesis grafting method was adopted for synthesis of Al grafted mesoporous silica (Al-
3
Page 3 of 18

MCM-41; Al-MS) [21]. The Al grafted MCM-41 samples (Al(n)-MS; where n = Si/Al molar
ratio) with Si/Al molar ratio of 20, 10 and 5 were synthesized as follows; MCM-41 (2 g) was
added to the solution containing required amount of aluminium iso-propoxide (0.338 g, 0.679
g and 1.368 g for Si/Al molar ratio of 20, 10 and 5, respectively) dissolved in 150 mL
toluene and the resulting mixture was allowed to stir at room temperature for 24 h. The solid
product was then filtered, dried at 90°C for 10 h and calcined at 550°C for 3h, which gives
Al-MS samples viz. Al(5)-MS, Al(10)-MS and Al(20)-MS. The materials were characterized
by ICP-AES, X-ray diffraction, N2 adsorption-desorption isotherm study and temperature
programmed desorption of NH3 (NH3 TPD) and the details of material’s characteristics have
already been reported in our previous research article [21].
2.3.
General procedure for N-alkylation of amines with alcohols using Al-MS
The amine and alcohol mixture was taken in a 50 mL reaction tube of reaction station (12
Place Heated Carousel Reaction Station, RR99030, Radleys Discovery Technologies, UK)
along with the catalyst activated at 180ºC for 2 h. The reaction mixture was allowed to stir
continuously (500 rpm) at definite temperature and for the required period of time. The
details of reaction conditions are given in the footnote of the tables and figures. After the
reaction, the reaction mixture was cooled to room temperature and diluted with
dichloromethane (5 mL). The reaction mixture was filtered to the catalyst and the reaction
mixture was analyzed by gas chromatography (Agilent 7890A) having a HP-5 (60m)
capillary column with a programmed oven temperature from 50 to 280ºC, 0.5 cm3/ min. flow
rate of N2 as carrier gas and FID detector. The conversion of alcohol was calculated on the
basis of its weight percent as follows;
Conversion (wt.%) of alcohol = 100 X [Initial wt.% of alcohol – Final wt.% of alcohol]/
Initial wt.% of alcohol.
The selectivity of the product was calculated as below,
4
Page 4 of 18

Selectivity (%) = 100 X peak area of product/ Ʃ Total peak area for all the products.
The products formed in the reactions were characterized by GC-MS analysis 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 discussion
3.1. Catalytic activity of Al-MS samples in N-alkylation of aniline with benzyl alcohol
Table 1. N-alkylation of aniline (1a) with benzyl alcohol (2a) using different catalysts.a
OH
H
NH2
N
N
Catalyst
N
+
+
+
1a
2a
3a
3a'
3a''
Selectivity (%)
Di-benzyl
Temp.
(°C)
Catalyst
2a conv. (%)
3a
3a' 3a''
ether
MS
16
11
24
76
-
100
85
80
-
-
-
-
-
-
-
-
Al(20)-MS
Al(10)-MS
Al(5)-MS
15
20
74
180
26
Al(5)-MS
Al(5)-MS
Al(5)-MS
200
210
220
100
99
100
88
85
70
2
0
1
8
13
27
2
2
2
Al(5)-MS b
Al(5)-MS c
Al(5)-MS e
99
99
72
96
98 (92)d
98
-
-
-
4
2
2
-
-
-
200
a1a/2a molar ratio = 1, 5 mmol 1a, 5 mmol 2a, 50 mg catalyst, 15 h.
b 1a/2a molar ratio = 1.5,
c 1a/2a molar ratio = 2,
d
1
isolated yield of 3a. The product (3a) was characterized by GC-MS and H NMR
spectroscopy [see ESI],
e 1a/2a molar ratio = 3.
Initially, the catalytic activity of Al-MS samples was examined for direct N-alkylation of
aniline (1a) with benzyl alcohol (2a) at 180°C (Table 1). The MS (without Al) did not give
5
Page 5 of 18

N-alkylated product (3a) and showed activity for imine formation giving 16% conversion of
2a to 100% imine product (3a’). The Al-MS samples showed good activity in N-alkylation of
aniline; the benzyl alcohol conversion and the selectivity towards N-alkylated product
gradually increased with increasing Al content, which can be attributed to increasing acidity
of the samples (see ESI, Table S1). The Al(5)-MS sample (Si/Al=5) gave highest conversion
of benzyl alcohol (76%) and selectivity to N-alkylated product (74%) showing its highest
activity for N-alkylation reaction. The results clearly indicate that the N-alkylation reaction is
catalyzed by acidic sites of Al-MS generated after Al grafting. The N-alkylation of aniline
(1a) with benzyl alcohol (2a) was also carried out using pure alumina as catalyst (reaction
condition: 10 mmol 1a, 5 mmol 2a, 50 mg catalyst, 200°C, 15h). The reaction resulted into
60% conversion of 2a to N-alkylated product (3a) showing that alumina is catalytically active
for the reaction. The dispersion of alumina grafted over MCM-41 surface (in Al(5)-MS)
enhances the number of catalytic active sites (acidic) for the reaction showing higher activity
(higher conversion of 2a; 99%) than pure alumina. The plausible mechanism of the N-
alkylation reaction over Al-MS is shown in Scheme 2(A). The benzyl alcohol molecules can
get adsorbed over the surface with the help of silanols and acid sites of Al-MS as shown in
structure I (Scheme 2(A)) [23–25]. The –OH group of benzyl alcohol can co-ordinate with
acidic sites (I; Scheme 2(A)), which will facilitate the –OH group removal by nucleophilic
attack of amine on benzylic carbon to give N-alkylated product. The adsorbed benzyl alcohol
may also produce benzyl carbonium ion (II; Scheme 2(A)) [24], which may subsequently
react with amine to form N-alkylated product. The imine formation with Al-MS or MS might
be occurring via oxidative dehydrogenation of benzyl alcohol to benzaldehyde, which can
react with aniline to form imine (Scheme 2(B)). The adsorbed benzyl alcohol molecule (I)
can get activated for oxidative dehydrogenation via alcoholate species (IV) to give
benzaldehyde (V). The silanols seem to be playing important role in activation of benzyl
6
Page 6 of 18

alcohol for oxidative dehydrogenation to benzaldehyde. This is also clearly evident from the
selective imine formation in amine-alcohol reaction with MS (with the help of surface
silanols) and gradually decreasing amount of imine with increasing Al grafting in Al-MS
samples. On increasing Al grafting, the surface silanols will be reduced, which will minimize
the oxidation of benzyl alcohol to benzaldehyde and therefore, imine formation will be less.
In our previous report on oxidative self coupling of benzyl amine [21], we had proposed that
the hydrogen bonding between –NH2 group of amine and silanols of MS activate the amine
substrate for oxidative dehydrogenation to imine intermediate, which reacts with amine to
form imine product.
At 200°C (Table 1), the benzyl alcohol conversion and selectivity to N-alkylated product
were significantly increased (100% and 88%, respectively), however di-N-alkylated product
(3a’’; 8%) and di-benzyl ether (2%) were also formed. Further increase in temperature
(220°C) reduced the selectivity for N-alkylated product (70%) due to di-N-alkylation of
aniline (3a’’: 27%). By increasing amine/alcohol molar ratio (Table 1) from 1 to 2, the
selectivity of N-alkylated product was enhanced to 98% at 200°C, which may be attributed to
increased concentration of nucleophile (aniline) in the reaction mixture. Further increase in
molar ratio (at 1a/2a molar ratio=3) decreased the conversion probably due to slow bulk
diffusion as well as adsorption of excess amine over active sites.
7
Page 7 of 18

(A)
H
Ph
H
H
O
Ph
N
(2a)
N

H2N Ph
1a
(3a)
(
)


O
H
O
O
H
H
H
O
H
O
H
H
Nucleophilic
reactn
H
H
H
H
H
H
O
O
O
O
O
O
Adsorption
of amine
Al-MS
= Acid site
(III)
(I)
*
C-O bond
fission
H2N Ph
(1a)
H
O
H
Nucleophilic
reactn
H
O
O
of amine
(II)
(B)
2a
(
)
H2N Ph
(1a)

Ph
N
Oxidative
dehydro-
genation
O2


O
O
(3a')
O
O
H
H
H
O
H
Nucleophilic H
reactn of amine
H
H
H
H
H
H
H
H
O-H bond
fission
O
O
O
O
O
O
O
O
O
Adsorption
MS or Al-MS
= Acid site
(V)
-H2O
I
( )
(IV)
*
Scheme 2. Plausible mechanistic pathway of (A) N-alkylation of aniline with benzyl alcohol
over Al-MS and (B) formation of imine over MS and Al-MS samples.
3.2.
N-alkylation of aniline with different alcohols using Al(5)-MS catalyst
The Al(5)-MS catalyst was also studied for N-alkylation of aniline with substituted benzylic
alcohols, primary and secondary alcohols. The results are indicative of good catalytic activity
of Al-MS catalyst in N-alkylation reactions with different types of alcohols (Table 2).
However, it was noticed that the alcohol’s nature (benzylic/ primary/ secondary and the
substituents in benzylic alcohols) influence the reactivity of alcohol in the using Al(5)-MS
catalyzed N-alkylation reactions. The N-alkylation of aniline with p-methoxy benzyl alcohol
(2b) resulted into 100% N-alkylated product; however the conversion of 2b was less (29%)
as compared to benzyl alcohol (2a; 99% conversion). The reaction of p-nitro benzyl alcohol
(2c) with aniline gave 100% imine product (3c’) with 60% conversion of 2c. This is very
interesting result clearly showing the effect of substituent’s nature (electron donating/
8
Page 8 of 18

withdrawing) on the reactivity and mode of reaction of benzylic alcohols. The electron
donating –OCH3 group in 2b may enhance the electron density on benzylic carbon reducing
its electrophilicity for reaction with nucleophile (amine) and therefore, 2b shows less
reactivity than 2a in the N-alkylation reaction. However, the conversion of 2b could be
increased to 67% by increasing the reaction temperature (at 220°C).
Table 2. N-alkylation of aniline with different alcohols using Al(5)-MS.a
R
H
NH2
N
R
+
N
R
N
R
Al(5)-MS
+
R
OH
+
1a
2
3
3'
3''
Alcohol (2)
Conv. (%)
Select. (%)
(3)
98
100
-
100
100
88e
(3’)
-
-
(3’’)
(2a) R: Ph-
99
2
-
-
-
-
-
(2b) R: pCH3O-Ph-
(2c) R: pNO2-Ph-
(2d) n-heptanol-
29, 67b
60
100
3, 25c, 35d
2, 26c, 74d
100c
-
-
-
(2e) Cyclohexanol
(2f) Butane-1,4-diol
HO
OH
a1a/2 molar ratio = 2, 10 mmol 1a, 5 mmol 2, 50 mg Al(5)-MS, 200°C, 15h.
bAt 220°C,
c1a/2 molar ratio = 1, 5 mmol 1a, 5 mmol 2, 50 mg Al(5)-MS, 200°C, 15h.
d1a/2 molar ratio = 1, 5 mmol 1a, 5 mmol 2, 100 mg Al(5)-MS, 200°C, 15h.
eProducts: 88% N-phenyl-2,3,4,5-tetrahydropyrrole (4) and 12% THF
N
Ph
O
THF
(4)
The electron withdrawing –NO2 group in 2c may facilitate the removal of hydrogen from –
OH group (making –OH group more acidic than 2a) with the help of surface basic sites. The
deprotonated alcohol or alkoxide species (adsorbed on the acidic sites) can undergo hydride
abstraction from benzylic carbon with the help of acidic sites (i.e. oxidative dehydrogenation)
giving carbonyl compound, which can readily react with aniline to form imine. The n-
heptanol (2d; primary alcohol) and cyclohexanol (2e; secondary alcohol) also showed good
reactivity with Al(5)-MS for N-alkylation of aniline giving 100% respective N-alkylated
products. The conversion of 2d and 2e was very poor (3% and 2%, respectively) when
9
Page 9 of 18

aniline/ alcohol molar ratio was 2; but the reaction using equimolar amount of aniline and
alcohol (2d/2e) under similar reaction condition increased the conversion to 25% and 26%,
respectively (Table 2). The reaction using equimolar amount of aniline and alcohol (2d/2e),
and higher catalyst loading (100 mg) gave enhanced conversion of 2d and 2e (35% and 74%,
respectively). The aniline molecules being basic in nature can be more adsorbable on acidic
sites as compared to the molecules of aliphatic alcohols (i.e., 2d and 2e) during the reaction.
At aniline/ aliphatic alcohol molar ratio of 2, the aniline concentration in reaction mixture
will be high, so more adsorption of aniline molecules on the acidic sites may reduce the
interaction of alcohol molecules with the catalytic sites slowing down the reaction. When
concentration of aniline in the reaction mixture is reduced by using equimolar amount of
aniline and alcohol (2d/ 2e) and by providing more catalyst, the adsorption of aniline can be
minimized as well as more sites will be available for alcohols to interact with the sites giving
enhanced conversion of alcohols. The catalysis results indicate the higher reactivity of
benzylic alcohols with Al-MS than primary and secondary aliphatic alcohols, which is
probably due to higher stability of carbonium ion or transition state of adsorbed benzylic
substrate. The butane-1,4-diol (2f) having two primary alcoholic –OH groups also showed
excellent reactivity for the reaction with aniline (di N-alkylation) giving 100% diol
conversion to cyclic N-alkylated product (4; 88% selectivity) in 15 h (Table 2). The
tetrahydrofuran (THF) is co-product, which is possible to be formed by acid catalyzed
cyclization of diol. The THF may also act as intermediate for the reaction with aniline to
form 4. This is evident from the decreasing selectivity of THF with time in the above reaction
(See ESI, Table S2) and significant conversion of THF (69% conversion into 4, after 5h)
itself in the Al(5)-MS catalyzed reaction of THF with aniline (See ESI, Table S3). The acidic
sites of Al(5)-MS may interact with THF through its ethereal oxygen (–O–) to facilitate the
nucleophilic attack of aniline on 2nd or 5th carbon of THF resulting into mono alkylated
10
Page 10 of 18

product. The amino group of mono alkylated product will do nucleophilic substitution of –
OH group (co-ordinated with acid site) of same molecule to form cyclic N-alkylated product
(4).
3.3.
N-alkylation of various amines with benzyl alcohol over Al(5)-MS catalyst
The Al(5)-MS showed good to excellent activity for N-alkylation of various amines with
benzyl alcohol (Table 3), however, it was observed that the nature of amine (basicity and
nucleophilicity) influenced the conversion and product selectivity. The electron donating –
OCH3 group reduced the reactivity of p-methoxy aniline (1b; 45% conversion) in N-
alkylation reaction as compared to aniline (1a), which may be attributed to higher basicity of
1b than 1a. Due to high basicity, the more adsorption of 1b over acidic sites of catalyst would
reduce the adsorption of 2a, which may slow down the reaction. This is also evident from less
conversion of alcohol (19%) with piperazine (1j; highly basic amine) to mono and di N-
alkylated products. The electron withdrawing –NO2 group in p-nitro aniline (1c) reduces its
basicity as well as nucleophilicity as compared to 1a and 1b. The less nucleophilic 1c could
not replace –OH group of the adsorbed benzyl alcohol (on acidic sites) during nucleophilic
reaction with aniline. Therefore, the adsorbed benzyl alcohol undergoes oxidative
dehydrogenation to benzaldehyde, which reacts with amine (1c) to give imine product
(100%). The formation of benzaldehyde in the reactions giving imine product is also a clear
evidence of alcohol dehydrogenation followed by amine coupling. In addition to amine
nucleophilicity, the reaction is also influenced by amine (nucleophile) concentration. For
instance, when equimolar amount of 1b (strong nucleophilic amine) and 2a were reacted, the
reaction resulted to imine formation. Even though 1b is highly nucleophilic but due to its
reduced concentration in equimolar reaction, the amine nucleophiles are not easily accessible
to the adsorbed alcohol molecules and therefore, alcohol undergoes dehydrogenation to form
benzaldehyde followed by amine coupling to imine product. It was interesting result that the
11
Page 11 of 18

weak nucleophilic amine 1c could also produce N-alkylated product (66%) with 89%
conversion of benzyl alcohol, when the molar amount of 1c was increased (four times). It
means that the less nucleophilic amine can also undergo the N-alkylation if higher amine
concentration is used in the reaction.
Table 3. N-alkylation of various amine substrates with benzyl alcohol using Al(5)-MS.a
OH
H
Al(5)-MS
N
N
R' NH2
+
+
R'
R'
1
2a
3
3'
Amine
Conv. (%)
Select. (%)
(3)
(3')
Others
(1a) R': Ph-
99
98
-
2b
1b
(
) R': p CH3O-Ph- 45
43c
100
-
-
93
-
7d
(1c) R': pNO2-Ph-
100
-
66
19
76
21
81
24d
4d
-
89e
58
1d
1e
(
(
) R': Ph-CH2-
) R': Ph-SO2-
97f
80
79
6
18
-
14d
3d
(1f) R': pCH3-Ph-SO2- 99f
(1g) R': Ph-CO-
(1h) Acetanilide
1i
97
78
19
81g
79g
14g
-
21
-
( ) Diphenyl amine 100
86h
-
(
) Piperazine
13
78i, 22j
-
1j
a1/2a molar ratio = 2, 10 mmol 1, 5 mmol 2a, 50 mg Al(5)-MS, 200°C, 15h;
bDi N-alkylated product;
c1b/ 2a molar ratio = 1;
dBenzaldehyde;
e1c/ 2a molar ratio = 4;
fAt 220°C;
gC-alkylation products (o- and p- derivatives);
hN-benzyl diphenyl amine (tert. amine);
iMono N-alkylated product;
jDi N-alkylated product
12
Page 12 of 18

In N-alkylation of benzyl amine (1d) with benzyl alcohol, the lesser conversion of alcohol
(58%) and selectivity of N-alkylated product (19%) may be due to high basicity of benzyl
amine and possibility of its self coupling reaction to form imine. The highly deactivated
amines like benzene sulphonamide (1e), toluene sulphonamide (1f), benzamide (1g) and
acetanilide (1h) also showed good reactivity in N-alkylation with benzyl alcohol (Table 3).
However, 1e and 1f required high temperature (220°C) to achieve 97-99% alcohol conversion
to respective N-alkylated products (79-80%). The diphenylamine (1i; secondary amine) could
also be converted to tertiary amine with 86% selectivity. With amides (1g and 1h), C-
alkylation products (mainly o- and p- benzylated products) were predominantly formed (79-
81%), which was also formed with diphenylamine (14%). The C-alkylation of these amine
substrates may be due to their poor nucleophilicity.
The study revealed that the acidity of Al-MCM-41, amine/alcohol molar ratio, reaction
temperature, alcohol’s and amine’s nature are major factors influencing the reaction. The
selective conversion of alcohols to N-alkylated amines can be achieved by optimizing the
above parameters for individual substrates. The high activity of Al-MCM-41for direct N-
alkylation is evident from its potential to activate the alcohols for reaction with deactivated
substrates (aniline and its derivatives).
3.4. Reuse of spent Al-MS catalyst
The spent Al(5)-MS catalyst (from N-alkylation of aniline with benzyl alcohol) was filtered
to separate from the reaction mixture. The spent catalyst was washed with acetone by stirring
in 5 ml acetone for 30 min and the washed catalyst was filtered and dried at 100°C for 2 h.
Thus regenerated catalyst was used in next reaction cycles under similar reaction condition to
examine the reusability of the catalyst. The regenerated catalyst showed similar activity to
fresh catalyst giving 97-99% conversion and 97-98% selectivity towards N-alkylated product
13
Page 13 of 18

for consecutive four reaction cycles (Table 4). It shows that Al-MS catalyst can be easily
regenerated by solvent washing and is reusable in N-alkylation reactions.
Table 4. Reusability of spent Al(5)-MS catalyst.a
Select. (%) of
Reaction cycle 2a Conv. (%)
3a 3a’ 3a’’
Fresh catalyst
99
99
98
98
97
98
98
97
98
97
-
2
1
2
1
1
I
II
III
IV
1
1
1
2
a1a/2a molar ratio = 2, 10 mmol 1a, 5 mmol 2a, 50 mg fresh/ regenerated catalyst, 200°C,
15h.
4. Conclusion
The Al-MCM-41 has potential for catalysis of N-alkylation of amines with alcohols
providing a very clean process (solvent free, base free, ligands free and without halides). The
catalyst acidity, reaction condition and reactants nature significantly influence the reaction.
The Al-MCM-41 (with Si/Al ratio of 5) was highly active for N-alkylation of various amines
and alcohols. The spent catalyst could be regenerated by solvent washing and reused
successfully.
Acknowledgement
Authors are thankful to Dr. H.M. Desai, Vice-Chancellor, DDU for providing necessary
facilities and Department of Science and Technology (DST), New Delhi, India for providing
financial support (No.: SR/FT/CS-051/2009) under Fast track scheme for young scientists.
References
[1] S. A. Lawrence, Amines: Synthesis, properties and application, ed. S. A. Lawrence,
Cambridge University Press, Cambridge, 2004.
14
Page 14 of 18

[2] (a) S. Bahn, S. Imm, L. Neubert, M. Zhang, H. Neumann, M. Beller, ChemCatChem 3
(2011) 1853–1864;
(b) G. Guillena, D.J. Ramo´n, M. Yus, Chem. Rev. 110 (2010) 1611–1641;
(c) M.H.S.A. Hamid, P.A. Slatford, J.M.J. Williams, Adv. Synth. Catal. 349 (2007) 1555–
1575.
[3] Y. Zhao, S.W. Foo, S. Saito, Angew. Chem. Int. Ed. 50 (2011) 3006–3009.
[4] Y. Du, S. Oishi, S. Saito, Chem. Eur. J. 17 (2011) 12262–12267.
[5] B. Blank, S. Michlik, R. Kempe, Chem. Eur. J. 15 (2009) 3790–3799.
[6] K.-i. Fujita, Z. Li, N. Ozeki, R. Yamaguchi, Tetrahedron Lett. 44 (2003) 2687–2690.
[7] T.T. Dang, B. Ramalingam, S.P. Shan, A.M. Seayad, ACS Catal. 2013, 3, 2536−2540.
[8] X. Yu, C. Liu, L. Jiang, Q. Xu, Org. Lett. 13 (2011) 6184–6187.
[9] X. Cui, Y. Zhang, F. Shi, Y. Deng, Chem. Eur. J. 17 (2011) 1021–1028.
[10] Y. Zhang, X. Qi, X. Cui, F. Shi, Y. Deng, Tetrahedron Lett. 52 (2011) 1334–1338.
[11] L. He, X.-B. Lou, J. Ni, Y.-M. Liu, Y. Cao, H.-Y. He, K.-N. Fan, Chem. Eur. J. 16
(2010) 13965 –13969.
[12] C.-P. Xu, Z.-H. Xiao, B.-Q. Zhuo, Y.-H. Wanga, P.-Q. Huang, Chem. Commun. 46
(2010) 7834–7836.
[13] A. Corma, T. Rodenas, M.J. Sabater, Chem. Eur. J. 16 (2010) 254–260.
[14] C. Gonzalez-Arellano, K. Yoshida, R. Luque, P.L. Gai, Green Chem. 12 (2010) 1281–
1287.
[15] J. He, J.W. Kim, K. Yamaguchi, N. Mizuno, Angew. Chem. 121 (2009) 10072–10075.
[16] J.W. Kim, K. Yamaguchi, N. Mizuno, J. Catal. 263 (2009) 205–208.
[17] T. Ishida, N. Kawakita, T. Akita, M. Haruta, Gold Bulletin 42 (2009) 267–274.
[18] M.M. Reddy, M.A. Kumar, P. Swamy, M. Naresh, K. Srujana, L. Satyanarayana, A.
Venugopala, N. Narender, Green Chem. (2013) DOI: 10.1039/C3GC41345D.
15
Page 15 of 18

[19] K. Motokura, N. Nakagiri, T. Mizugaki, K. Ebitani, K. Kaneda, J. Org. Chem. 72 (2007)
6006–6015.
[20] (a) A.C. Carmo Jr., L.K.C. de Souza, C.E.F. da Costa, E. Longo, J.R. Zamian, G.N. da
Rocha Filho, Fuel 88 (2009) 461–468;
(b) B.R. Jermy, A. Pandurangan, Appl. Catal. A: Gen. 288 (2005) 25–33;
(c) M Selvara, A Pandurangan, K.S Seshadri, P.K Sinha, V. Krishnasamy, K.B Lal, J. Mol.
Catal. A: Chem. 186 (2002) 173–186;
(d) K.G. Bhattacharyya, A.K. Talukdar, P. Das, S. Sivasanker, J. Mol. Catal. A: Chem. 197
(2003) 255–262;
(e) B.R. Jermy, A. Pandurangan, J. Mol. Catal. A: Chem. 256 (2006) 184–192;
(f) K. Chaudhari, R. Bal, A.J. Chandwadkar, S. Sivasanker, J. Mol. Catal. A: Chem. 177
(2002) 247–253;
(g) E. Antonakou, A. Lappas, M.H. Nilsen, A. Bouzga, M. Stocker, Fuel 85 (2006) 2202–
2212;
(h) E.F. Iliopoulou, E.V. Antonakou, S.A. Karakoulia, I.A. Vasalos, A.A. Lappas, K.S.
Triantafyllidis, Chem. Engg. J. 134 (2007) 51–57.
[21] K.N. Tayade, M. Mishra, J. Mol. Catal. A: Chem. 382 (2014) 114–125.
[22] G. Cami-Kobeci, P.A. Slatford, M.K. Whittlesey, J.M.J. Williams, Bioorg. Med. Chem.
Lett. 15 (2005) 535–537.
[23] B. Granqvist, T. Sandberg, M. Hotokka, J. Colloid Interface Sci. 310 (2007) 369–376.
[24] M.H.C. de la Cruz, M.A. Abdel-Rehim, A.S. Rocha, J.F.C. da Silva, A. da Costa Faro
Jr., E.R. Lachter, Catal. Commun. 8 (2007) 1650–1654.
[25] K. Ganesan, C.N. Pillai, J. Catal. 119 (1989) 8–13.
16
Page 16 of 18

Graphical abstract
Solvent free acid catalyzed direct N-Alkylation of amines with alcohols using Al grafted
MCM-41
Kamlesh N. Tayade1, Manish Mishra1,* Munusamy K.,2 , Rajesh S. Somani2
1Department of Chemical Engineering And Shah-Schulman Center for Surface Science and Nanotechnology,
Faculty of Technology, Dharmsinh Desai University, College Road, Nadiad – 387 001, Gujarat, India.
E-mail: manishorgch@gmail.com: Fax: +91 268 2520501; Tel.: +91 268 2520502.
2Discipline of Inorganic Materials and Catalysis, Central Salt and Marine Chemicals Research Institute
(CSMCRI), Council of Scientific and Industrial Research (CSIR), GB Marg, Bhavnagar 364002, Gujarat, India.
The Al grafted MCM-41 (Si/Al=5) showed good to excellent activity in solvent free acid
catalyzed direct N-Alkylation of amines with alcohols giving selective conversion to N-
alkylated amines.
17
Page 17 of 18

Research highlights
1) Al grafted MCM-41 showed potential of direct N-alkylation of amines with alcohols.
2) Solvent free and base/ promotor free N-alkylation method was established.
3) Effect of catalyst acidity, reaction conditions and substrates nature were studied.
4) Benzylic, primary and secondary alcohols were activated for N-alkylation reaction.
5) Deactivated amine substrates could also be alkylated by alcohols.
18
Page 18 of 18