Alkaline carbons as effective catalysts for the microwave-assisted synthesis of N-substituted-gamma-lactams

Article abstract of DOI:10.1016/j.apcata.2011.03.017

The selective construction of new CC or Cheteroatom bonds is frequently the fundamental step in the synthesis of derivatives with high added value. In particular, molecules with CN bonds are of great interest due to their widespread use and intrinsic impo

Full text of DOI:10.1016/j.apcata.2011.03.017

Applied Catalysis A: General 398 (2011) 73–81
Contents lists available at ScienceDirect
Applied Catalysis A: General
journal homepage: www.elsevier.com/locate/apcata
Alkaline carbons as effective catalysts for the microwave-assisted synthesis of
N-substituted-gamma-lactams
V. Calvino-Casildaa,∗, R.M. Martín-Arandab, A.J. López-Peinadob
a Catalytic Spectroscopy Laboratory, Instituto de Catálisis y Petroleoquímica (CSIC), Marie Curie 2 E-28049 Madrid, Spain
b Dpto. Química Inorgánica y Química Técnica. Universidad Nacional de Educación a distancia (UNED), Senda Del Rey 9 E-28040 Madrid, Spain
a r t i c l e i n f o
a b s t r a c t
Article history:
The selective construction of new C C or C heteroatom bonds is frequently the fundamental step in
the synthesis of derivatives with high added value. In particular, molecules with C N bonds are of great
interest due to their widespread use and intrinsic importance. Of the large number of organic compounds
with useful biological activity, organic compounds with C N bonds are among the most prominent. For
instance, the nitrogenated gamma-lactamic heterocycles are the basic structures of many substances
used as intermediates in the synthesis of important compounds with pharmacological properties such
as psychotropics and antihypertensives as well as others with biological properties. In the present
work, we reported for the first time an efficient and eco-friendly alternative to obtain N-substituted-
gamma-lactams by carbon–nitrogen coupling of 2-pyrrolidinone and 1-heptanal assisted by microwave
irradiation, over activated alkali-Norit carbon catalysts in solvent-free conditions.
Received 21 December 2010
Received in revised form 7 March 2011
Accepted 9 March 2011
Available online 17 March 2011
Keywords:
Activated carbons
Heterogeneous catalysis
Microwave activation
Green chemistry
© 2011 Elsevier B.V. All rights reserved.
2-pyrrolidinone
N-substituted-gamma-lactams
1. Introduction
One of the approaches for achieving the fundamental scientific
challenges of green chemistry is to explore alternative reaction
The synthesis of derivatives with high added value (Fine Chem-
icals) as well as the production of commodity and special polymers
requires a fundamental step based mainly on the selective con-
struction of new C C or C heteroatom bonds. In particular, among
the large number of organic compounds with useful biological
activity, organic compounds with C N bonds are one of the most
prominent. For instance, the construction of C N bonds by N-
subtititution of nitrogenated heterocycles as gamma-lactams, is of
great interest since they are the basic structures of many intermedi-
ates used in the synthesis of compounds with important biological
properties as kaitocephalin, lemonomycin and aeuroginosin [1–3]
and others with pharmacological properties related to the area of
neuroexcitatory chemistry [4] as psychotropics, antihypertensives
and compounds with antimuscarinic activity [5–10]. The function-
alized gamma-lactams including functionalized pyrrolidinones not
only have antibacterial properties but have also recently been used
as promoters of conformation control of peptides [11–14] as well
as intermediates for the synthesis of agrochemicals, textile aux-
iliaries, solvents, polymers, stabilizers, dyes and nylon precursors
[15,16].
conditions and reaction media to accomplish the desired chemical
transformations with minimal by-products, as well as eliminating
the use of conventional organic solvents [17]. Some of these impor-
tant alternative tools include the use of microwave irradiation.
Microwave-assisted chemical reactions are accelerated because of
selective absorption of MW energy by polar molecules. The short
reaction time, and expanded reaction range that is offered by MW
assisted synthesis are suited to the increased demands in industry,
in particular, in the pharmaceutical industry [18–21].
The objective of this contribution is to demonstrate that
the carbon–nitrogen (hetero) coupling reaction between gamma-
lactams (2-pyrrolidinone) and aldehydes (1-heptanal) (Scheme 1)
can be carried out successfully combining carbon catalysts and
microwave activation in absence of any solvent. Under mild con-
ditions, the authors have developed a remarkable fast one-pot
synthesis of N-substituted-gamma-lactams. Kinetics and mecha-
nism of the reaction as well as the influence of external reaction
parameters such as basicity (alkaline promoter supported on the
carbon) have been also investigated comparing the results obtained
under microwave activation with those obtained under conven-
tional thermal activation.
In the literature is described that N-␣-hydroxialkylated-lactams
of type A (Scheme 1) are the main reaction product obtained in
the carbon–nitrogen (hetero) coupling reaction over basic cata-
lysts under conventional thermal activation [10]. In the present
∗
Corresponding author. Tel.: +34 915854879.
E-mail address: vcalvino@icp.csic.es (V. Calvino-Casilda).
0926-860X/$ – see front matter © 2011 Elsevier B.V. All rights reserved.
doi:10.1016/j.apcata.2011.03.017

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V. Calvino-Casilda et al. / Applied Catalysis A: General 398 (2011) 73–81
O
O
O
OH
basic carbon
MW
-H2O
N
C6H13CHO
N
CH
NH
+
C6H12
C6H13
A
B
Scheme 1. N-substitution of 2-pyrrolidinone with 1-heptanal under microwave activation over basic carbon catalysts.
sphere (He, 100 cm3/min) from room temperature to 1000 ◦C with
a heating ramp of 1 ◦C/min. The thermal analysis instrument SDT
Q600 was coupled to a mass spectrometer cuadrupolar Balzers
THERMOSTAR (TG-DTG-MS) registering qualitative and quantita-
tively the gases released during the analysis of each sample. The
ash contents of the catalysts were also obtained by using these
techniques. For this, the experiments were carried out flowing air
(100 mL/min) from room temperature to 1000 ◦C with a heating
ramp of 5 ◦C/min.
The chemical state and the relative dispersion of the alkali met-
als deposited on the surface of the carbon of the samples were
determined by X-ray photoelectron spectroscopy (XPS). Photo-
electron spectra (XPS) were acquired with a VG ESCALAB 200R
spectrometer equipped with a hemispherical electron analyzer
and MgK␣ (hꢀ = 1253.6 eV, 1 eV = 1.6302 × 10−19 J) X-ray source.
The powder samples were pressed into aluminum holders and
mounted on a sample rod placed in the pretreatment chamber of
the spectrometer. After outgassing 1 h at room temperature, they
were placed into the analysis chamber. The residual pressure in the
ion-pumped analysis chamber was maintained below 5 × 10−9 Torr
during data acquisition. The intensities of C 1s, O 1s, and Na 1s or Cs
3d5/2 peaks were estimated by calculating the integral of each peak
after smoothing and subtraction of the “S”-shaped background and
fitting the experimental curve to a combination of Gaussian and
Lorentzian lines of variable proportion. The binding energies (BE)
were reference to the major C 1s component at 284.9 eV, this ref-
erence giving BE values with an accuracy of 0.1 eV.
work, the use of alkali-activated carbons as catalysts led selec-
tively to N-1-heptenyl-2-pyrrolidinone (B) by dehydration of
N-␣-hydroxiheptanyl-2-pyrrolidinone A (Scheme 1).
Activated carbons have been used to catalyze efficiently organic
synthesis, because of their extended surface area, microporous
structure, and high degree of surface reactivity [22]. In addition, the
inclusion of alkaline promoters on the carbons results in the gener-
ation of basic sites on their surfaces [23–26]. Alkaline carbons may
also be appropriate solids to selectively catalyze basic reactions.
The microwave irradiation, in combination with alkaline carbons
provides in very short times and very mild conditions of reactions
an interesting reactivity and peculiar selectivity, being an environ-
mentally friendly process: 82% conversion and 100% selectivity in
1 min under microwaves at 600 W (381–388 K) over Na-Norit cat-
alysts. In contrast, 4 h in batch reactor at 307 K are necessary to
achieve 79% conversion and 100% selectivity.
2. Experimental
2.1. Catalyst preparation
Three alkaline carbon catalysts (Na-Norit, Cs-Norit and NaCs-
Norit) have been prepared by impregnation of a pristine activated
carbon RX-1.5-EXTRA Norit with the corresponding aqueous alka-
line chloride solution (2 M for monometallic carbons, and 1 M of
each metal chloride solution for the bimetallic carbon) at 358 K for
70 h, using a liquid/solid ratio of 10. The samples were filtered and
washed with distilled water until chloride free. After drying at 383 K
for 48 h the resulting carbons were pelletized, crushed and sieved
to particle size Ø < 0.140 mm diameter.
The contents in carbon, hydrogen, and nitrogen of the acti-
vated Norit carbon and of the alkali-Norit carbon catalysts were
determined by elemental analysis using the atomic absorption
spectroscopy with a Microanalyzer Perkin Elmer CHN 2400 equip-
ment.
2.2. Catalyst characterization
The basic carbons were also characterized by XRD using a Seifert
C-3000 diffractometer with radiation Cu K␣ (ꢁ = 0.154 nm) and
by using inductively coupled plasma mass spectrometry (ICP-MS)
using a equipment Elan 6000 Perkin-Elmer Sciex with autosampler
AS91, a Millipore water purification system Milli-Q Element and
a microwave oven Milestone ETHOS PLUS for the digestion of the
samples. The ICP-MS technique allows to analyze qualitatively and
quantitatively the presence of trace metals.
TPD experiments were performed in a continuous flow appa-
ratus, at atmospheric pressure, using a flow of 20 mol% CO2 in
helium. Prior to adsorption, each sample (ca. 300 mg) was kept
under helium flow, at 623 K, until the complete removal of the
adsorbed impurities. The sample was cooled down to 298 K and,
using a sampling valve, pulses of the adsorbing gas were intro-
duced. The physisorbed gas was removed by passing helium for
30 min. The thermodesorption was then performed by heating the
sample at 10 K/min under helium flow (1 mL/s).
The basicity of the alkali carbon catalysts was also studied by
using the Knoevenagel probe reaction between benzaldehyde and
malonic esters of different pKa (ethyl cyanoacetate, pKa = 9; ethyl
acetoacetate, pKa = 10.7; diethyl malonate, pKa = 13.3 and ethyl bro-
moacetate, pKa = 16.5). The reaction was carried out in a batch
reactor using three different reaction temperatures (393, 413 and
433 K).
The alkali-loaded catalysts Na-Norit, Cs-Norit and the bimetallic
NaCs-Norit were characterized following different physicochemi-
cal techniques. The pH measures of the catalysts were calculated by
aqueous suspensions of the carbon samples, 1 g portions of carbon
were mixed with 20 cm3 of distilled water; the suspensions were
shaken mechanically for 48 h at 298 K and then their pH values
were determined using a glass electrode, Omega pH-meter, model
PHB-62 [27].
Specific surface areas and adsorbed volume of the carbon
samples were determined by N2 adsorption isotherms at 77 K
applying the BET method [28] and CO2 adsorption at 273 K applying
Dubinin–Radushkevich and Dubinin–Astakhov methods [161] in a
Micromeritics ASAP 2010 Volumetric System. The samples were
pre-treated in situ under vacuum at 573 K for 8 h. Volume adsorbed
in the different types of pores was calculated by the DFT (Density
Functional Theory) method [29] by means of DFT plus software.
Thus, carbon dioxide adsorption allows to determine the volume
of narrow micropores of the samples while nitrogen adsorption
supplies the total volume of the micropores.
To study the thermal stability of the pristine support (acti-
vated Norit carbon RX-1.5) and the alkali-Norit catalysts (Na-Norit,
Cs-Norit and NaCs-Norit), thermogravimetric analysis (TG) and
differential thermal analysis (DTG) were carried out in inert atmo-

V. Calvino-Casilda et al. / Applied Catalysis A: General 398 (2011) 73–81
75
2.3. Reaction procedure
2.3.1. Microwave activation
Activity and selectivity of the catalysts under microwave acti-
vation were determined using a multimode microwave oven. The
reaction was carried out in a sealed microwave PTFE Teflon vessel.
The microwave equipment employed in this work is a SAMSUNG
M-1827-N multimode microwave oven operated at the fixed-
frequency of 2450 MHz.
The gamma-lactam 2-pyrrolidinone (2 mmol) and the alkali
carbon (10 wt%) were blended in the Teflon vessel and an
equimolecular amount of 1-heptanal was added in absence of any
solvent. The mixture was irradiated in the microwave oven at
600 W of power for 1–5 min. The temperature during the reaction
was measured through the Teflon vessel walls using an infrared
probe, Ventix 8889, range T −40 to +500 ◦C, ꢁ = 670 nm, laser
pointer, response time 500 ms. The reaction was followed using
an Agilent 6890 gas chromatograph (GC) equipped with a 60 m
long BP1 capillary column. The mass spectra of the products were
obtained on a Hewlett-Packard HP5971A spectrometer. The reac-
tivity is expressed in terms of the amount of B obtained in wt%.
After cooling, the reaction products were extracted with acetone
(20 mL) and filtered. The isolated catalyst was then washed with
acetone and distilled water and dried at 150 ◦C for 2 h to be reused
in a new cycle of reaction.
2.3.2. Conventional thermal heating
A mixture of gamma-lactam 2-pyrrolidinone and 1-heptanal
was heated in a batch reactor while stirring and in absence of any
solvent. After five minutes, the catalyst was added to the reaction
mixture and the reaction time started. After cooling, the reaction
products were extracted with acetone (20 mL) and filtered. The
reaction was followed by gas chromatography–mass spectrome-
try (GC–MS). The reactivity is expressed in terms of the amount of
B obtained in wt%.
Fig. 1. N2 adsorption isotherms at 77 K and CO2 adsorption isotherms at 273 K of
the Norit support and the alkali-Norit catalysts (Na-Norit, Cs-Norit and NaCs-Norit).
3. Results and discussion
3.1. Catalyst characterization
ume of nitrogen of 0.571 cm3/g (Table 1). The pore size distribution
of this carbon is principally micropores (81.8%) with an important
contribution of mesopores (16.5%). The impregnation of the pristine
carbon with different alkali chlorides does not change significantly
the specific surface area characteristics of the support (Table 1).
The catalysts show slight differences in the total volume of micro-
pores. The Cs-Norit catalyst presents the higher value of surface
area and nitrogen adsorption into the micropores. To study the nar-
row microporosity in solids by CO2 adsorption, different equations
can be used, being the Dubinin–Radushkevich (D–R) equation the
most frequently used [30]. When the microporous structures are
not homogeneous, the Dubinin–Astakhov (D–A) equation is used
[30]. Table 1 shows the values of the microporous area and the vol-
ume of the micropores calculated using both equations, D–R and
D–A. It can be verified from these results that the microporous
Fig. 1 illustrates the nitrogen adsorption isotherms at 77 K and
CO2 adsorption isotherms at 273 K. It must be emphasized that the
main characteristic of an activated carbon, apart from its high sur-
face area, is its microporosity. The analysis of the gas adsorption
isotherms in activated carbons provides a first approximation to
their microporous structure employing adsorbants such as nitro-
gen (77 K) and carbon dioxide (273 K). It has been verified that
carbon dioxide adsorption allows the determination of the vol-
ume of narrow micropores while nitrogen adsorption supplies the
total volume of the micropores. Table 1 shows specific surface areas
(BET) and distribution of the pore volume obtained from nitrogen
adsorption at 77 K for the samples. The Norit pristine carbon has
a high specific surface area (1450 m2/g) with a total adsorbed vol-
Table 1
(a) BET specific surface areas and distribution of the pore volume obtained from N2 adsorption at 77 K and (b) microporous area and volume of micropores obtained from
CO2 adsorption at 273 K for the pristine Norit carbon and the alkali-Norit carbons.
Catalyst
N2 adsorption
CO2 adsoprtion
*
*
*
*
SBET (m2/g)
Vmicropore (cm3/g)
Vmesopore (cm3/g)
Vtot (cm3/g)
Smicropore(D–R)
(m2/g)
Vmicropore(D–R)
(cm3/g)
Smicropore(D–A)
(m2/g)
Vmicropore(D–A)
(cm3/g)
Norit
1450
1375
1447
1338
0.467 (81.8%)
0.440 (77.2%)
0.460 (84.7%)
0.434 (78.2%)
0.094 (16.5%)
0.111 (19.5%)
0.074 (13.6%)
0.104 (18.7%)
0.571
0.570
0.543
0.555
554
300
370
460
0.201
0.109
0.135
0.167
683
255
363
508
0.272
0.092
0.135
0.192
Na-Norit
Cs-Norit
NaCs-Norit
*
Calculations were carried out using the Dubinin–Radushkevich (D–R) equation and the Dubinin–Astakhov (D–A) equation with the data obtained from CO2 adsorption.

76
V. Calvino-Casilda et al. / Applied Catalysis A: General 398 (2011) 73–81
Table 2
Ph, thermogravimetric analysis (TG), elemental analysis and quantitative elemental analysis (ICP-MS) of the carbon catalysts.
Catalyst
pH
Ash (%)
M2Oa
Metal
%C
%H
%N
%O
Analyte concentration (ppm)
(at-g/100 g cat)
Na
Cs
Norit
7.05
7.17
7.58
7.51
4.3
5.1
5.2
5.4
–
–
90.50
88.82
87.94
89.12
0.38
0.52
0.60
0.50
0.45
0.45
0.47
0.46
4.37
5.11
5.79
4.52
305.17 (0.030%)b
602.26 (0.06%)b
478.95
1.58 (0.0002%)b
0.39
Na-Norit
Cs-Norit
NaCs-Norit
0.8
0.9
1.1
0.013
0.003
–
790.40 (0.08%)b
407.78 (0.04%)
554.91 (0.05%)b
a
Difference (ash content), M – Alkali metal.
The values enclosed in brackets represent weight percentage of the correspondent analyte.
b
specific surface area of the support decreases when it is impreg-
nated with the corresponding alkali salt as the metallic cations (Na+,
Cs+) deposit on the microporous surface of the carbon.
percentage of the corresponding alkali metal supported in each cat-
alyst. The results showed that the exchange capacity of Norit RX-1.5
EXTRA carbon for sodium (ionic radius = 0.095 nm) is around four
times the exchange capacity for cesium (ionic radius = 0.169 nm)
due to the higher diffusional barrier that Cs+ ions has to overcame
to access the interior of the micropores of the carbon support.
The chemical state and the relative dispersion of the alkaline
metals at the surface of the carbon of the different samples were
determined by XPS. Table 3 shows the BEs of C 1s and O 1s core
levels, and the characteristic inner levels of the alkaline elements,
together with the M/C atomic ratios, determined from the peak
intensities and the tabulated sensitivity atomic factors [34]. Gen-
erally, all the samples showed that the C1s core level presented
three peaks; the first peak at 284.5 eV due to the ꢀC Cꢁ bonds of the
From Fig. 1 it can also be appreciated that the adsorption of
CO2 at 273 K is lower than the adsorption of nitrogen at 77 K. This
indicates the absence of narrow micropores in the structure of the
solid catalysts prepared. The CO2 adsorption isotherms of the NaCs-
Norit catalysts show a higher adsorption of CO2 than the rest of
the catalysts because the metallic cations mostly deposit on the
surface during the impregnation, without entering the microporous
structure of the carbon. These results were contrasted using other
techniques, such as XPS, the results are shown below.
Table 2 summarizes the pH of the alkali-doped activated car-
bons catalysts (Na-Norit, Cs-Norit and NaCs-Norit). The pristine
carbon, RX-1 EXTRA Norit, exhibits a pH of 7.05, which increases
only slightly in the sample supported with sodium or/and cesium
respectively in the range 7.17–7.51.
The thermal analysis (TG-DTG-MS) obtained for the alkali-Norit
catalysts and the pristine Norit carbon, showed similar profiles
when they were under heating process in inert atmosphere. The
alkali-Norit catalysts showed a higher loss in weight than the pris-
tine Norit support (Norit, 6.94%; Na-Norit, 8.85%; Cs-Norit, 8.01%;
NaCs-Norit, 8.40%) taking into account the decomposition of the
new oxygenated surface groups which were formed during the
manipulation of the samples as a consequence of the reoxidation
of the carbon surface, as well as the formation of the oxide and
carbonate species form in the structure of the carbon during the
impregnation. Fig. 2 shows the spectra for the pristine support and
one of the carbon catalysts prepared, Cs-Norit. The weight losses
below 500 ◦C approximately can be principally attributed to carbon
dioxide and water. The weight loss as water is normally due to the
water adsorbed on the surface during the manipulation of the sam-
ples. If the weight loss happens at temperatures higher than 100 ◦C,
then it is related with the dehydration of alcohol and phenol groups
that are present on the surface of the carbon. The thermograms
obtained for the samples show that below 100 ◦C the weight loss
was due to CO2 and H2O molecules enclosed in the porous structure
of the carbon. The more sensitive surface oxygenated groups were
removed at temperatures below 300 ◦C approximately, and they
included acidic groups such as carboxiles, lactones and anhydrides
[31,32]. The weight loss that occurred approximately at tempera-
tures above 700 ◦C was attributed to a loss of oxygenated surface
groups with a weak acidic, neutral or basic character such as ether,
phenol, carbonyl, quinone and pyrone groups. It could also be due
to a rupture in the molecular structure of the carbon by expulsion of
gases such as hydrogen, carbon dioxide and hydrocarbons. At tem-
peratures higher than 1000◦ C, it can be affirmed that practically all
the oxygenated surface groups have decomposed [33].
Norit
100
99
98
97
96
95
94
93
92
91
90
0,06
0,05
0,04
0,03
0,02
0,01
0,00
TG
DTG
m/z=44 (CO2)
m/z=18 (H2O)
m/z=2 (H2)
100000
10000
1000
100
10
1
0,1
0,01
0
100
200
300
400
500
600
700
800
900
1000
Temperature (ºC)
Cs-Norit
0,06
0,05
0,04
0,03
0,02
0,01
0,00
100
99
98
97
96
95
94
93
92
91
90
m/z=44 (CO2)
m/z=18 (H2O)
m/z=2 (H2)
TG
DTG
1000000
100000
10000
1000
100
10
1
0,1
Table 2 shows the results obtained from the thermogravimet-
ric analyses of the samples calcined in air flow (100 mL/min) at
1000 ◦C. The Norit carbon sample showed content in ash of 4.3%;
this content in ash was higher in the alkali-Norit carbon samples.
The difference in the content of ash of the impregnated carbons
and the pristine carbon without treatment was used to calculate the
0,01
0
100
200
300
400
500
600
700
800
900
1000
Temperature (ºC)
Fig. 2. Thermograms obtained by thermal and mass analysis (TG-DTG-MS) of the
pristine Norit carbon and Cs-Norit catalyst. Heating ramp: 1 ◦C/min until 1000 ◦C,
He flow = 100 mL/min.

V. Calvino-Casilda et al. / Applied Catalysis A: General 398 (2011) 73–81
77
Table 3
Binding energies (eV) of the internal electrons and surface atomic relations of the basic alkali-Norit carbons.
Catalyst
C 1s
O 1s
M 1s (2p, 3d)
Ototal/Ctotal at
0.040
Atomic relation Cs/C
284.5 (65)
285.9 (25)
288.0 (10)
531.8 (59)
533.5 (41)
–
–
Norit
284.5 (62)
285.9 (27)
288.0 (11)
Na-Norita
531.8 (51)
533.5 (49)
–
0.075
0.093
0.080
–
284.5 (62)
285.9 (27)
288.0 (11)
531.7 (49)
533.5 (51)
727.4
727.5
0.004
0.005
Cs-Norit
284.5 (63)
285.9 (27)
288.0 (10)
NaCs-Norita
531.8 (45)
533.5 (55)
The values in parentheses indicate the % of each peak.
a
No sodium was detected.
carbon structure or to the non-functionalized CH species which
still conserved hydrogen atoms, the second peak approximately at
285.9 eV showing approximately a 25–39% contribution to the total
area due to C O species, and the third peak at 288.0 eV, with lower
rior of the micropores, is higher, and therefore they tend to stay
on the surface. It was not possible to detect Na+ on the surface
of the carbon for the Na-Norit sample since its low charge/radius
relation allowed it to access the interior of the porous structure
of the carbon and its small radius allowed it to enter the microp-
ores. Although Cs-Norit sample has a lower charge/radius relation
than Na+, it was possible to detect the presence of Cs on the
surface since this cation found a greater difficulty in accessing
the micropores due to its higher radius. These data were con-
trasted with the ones obtained by thermal analysis and surface area
measurements.
The results obtained by atomic absorption spectroscopy are
shown in Table 2. From these results and knowing the ash content in
the samples by thermal analysis (Table 2), the amount of oxygen in
each sample was calculated by subtraction. Generally, the percent-
age in oxygen increased slightly in the impregnated carbon samples
compared to the pristine Norit carbon. This increase was due to the
presence of a higher number of oxygenated surface groups in the
carbon structure of the alkali-Norit catalysts as a consequence of a
reoxidation of their surface during their manipulation.
intensity corresponds to the functional groups that contain ꢀC
O
species.
The nature of the oxygenated surface groups that were present
on the carbon surface of the samples was determined through the
values of the bond energies of core level O1s. In the O1s level there
were two peaks, one of them, near 531 eV, was due to species of
type C O (carboxyl and lactone groups) of the carbon support; the
other peak, near 533 eV, is due to species of type C O− (phenol or
ether group) belonging to the structure of the carbon and possi-
ble oxide species formed when the alkali or alkaline earth species
interacted with the surface oxygenated groups present in the struc-
ture of the carbon. In Table 3 the percentage corresponding to this
peak grew with respect to the peak of the pristine Norit carbon for
the alkali-Norit samples, confirming the formation of oxide-type
species in the treated carbons. In addition, the binding energies of
the internal electrons of the alkali/alkaline earth atoms adjusted to
oxide type species although the binding energies of the carbonate
type species are very similar and therefore the presence of a small
proportion of these types of species could not be discarded. These
carbonate type species would be originated by the formation of
alkali metal-oxygen groups which would have been formed when
the metallic cations react with the surface oxygenated species of
the surface of the carbon which would next have been oxidized
during the manipulation of the samples. The Ototal/Ctotal relation
is showed in Table 3, which indicated the degree of oxidation of
the surface of the samples. Observing these values, it is seen that
the content in oxygen increased in the treated carbons, which con-
firmed the formation of new oxygenated groups on the surface of
the samples, oxygenated surface groups of the carbon structure and
alkali/alkaline earth oxide and/or carbonate species.
The X-ray diffraction spectra (XRD) of the Norit support and the
basic alkali-Norit carbons are illustrated in Fig. 3. X-ray diffraction
and the diffraction patterns from the JCPDS (Joint Committee on
Powder Diffraction Standards) of the ICDD (International Center
* Graphitic carbon
*
*
*
Cs-Norit
*
*
Table 3 also shows the concentration of the alkali elements that
were incorporated in the activated Norit carbon used to prepare
the alkali-Norit samples. In order to calculate this, the intensi-
ties of the peaks, corrected by the atomic sensitivity factors, were
measured. The results show that the M/C relation was not high
(0.003–0.012). During the adsorption-impregnation process, the
M+ cations (catalysts Na-Norit and NaCs-Norit, Na+; Cs-Norit and
NaCs-Norit, Cs+) would interact by electrostatic forces with the sur-
face groups present on the surface of the carbon. However, when
accessing the sites located in the micropores of the substrate and
due to steric hindrance, two important variables had to be taken
into account: ionic radius and the charge of the cation (polariza-
tion capacity charge/radius). As the charge/cation radius increases,
the diffusion barrier, which has to be overcome to access the inte-
*
Na-Norit
NaCs-Norit
Norit
*
*
10
20
30
40
50
60
70
80
90
2 (º)
Fig. 3. XRD of the Norit support and Na-Norit, Cs-Norit, NaCs-Norit carbon catalysts.

78
V. Calvino-Casilda et al. / Applied Catalysis A: General 398 (2011) 73–81
for Diffraction Data), did not show the presence of alkali chlo-
rides in the structure of the carbon, which could have stayed in
the structure after impregnating the pristine Norit support during
the preparation of the alkali-Norit samples. The XRD diffractogram
corresponding to the pristine Norit support showed very low inten-
sity peaks corresponding to graphitic carbon. After impregnating
the pristine Norit support, the XRD spectra of the Na-Norit, Cs-Norit
and NaCs-Norit samples showed no additional peaks corresponding
to carbonate and/or metallic oxide species, as they were by XPS.
The ICP-mass technique was used to characterize both qual-
itatively and quantitatively the inorganic species (trace metals)
present in the pristine Norit as well as in the alkali-Norit car-
bons (Na-Norit, Cs-Norit and NaCs-Norit). The results obtained
in the quantitative analysis of metals Na and Cs involved in the
preparation of the basic carbon catalysts are shown as analyte con-
centration (ppm) in Table 2. The qualitative analysis of the samples
show the presence of trace metals such as B, Mg, Al, K, Ca, Fe, Ti, Bi,
V, Mn, Zn and Ba.
Fig. 4 shows the TPD profiles of the pristine Norit carbon and the
alkali-Norit samples. For the pristine carbon a “shoulder” at 570 K
was detected due to the decomposition of superficial groups. For
Cs-Norit and NaCs-Norit catalysts, a band in the range 350–550 K
was detected and this band is stronger in case of Cs-Norit cata-
lyst. For NaCs-Norit catalyst, a “shoulder” in the range 550–750 K
was also detected. For Na-Norit catalyst, a weak “shoulder” in the
range 600–800 K was detected. The deconvolution of these curves
showed that three types of basic sites might be considered: weak
(420 K), medium strength (500 K) and strong basic sites (700 K). It
can be concluded that Cs-Norit is mainly composed by weak basic
sites, NaCs-Norit shows both weak and strong basic sites and Na-
Norit presents strong basic sites. Considering the activity results
obtained in the studied reaction for all the samples, the activity of
the reaction can be assigned to weak basic sites present mostly in
Cs-Norit catalysts and lesser in NaCs-Norit catalysts.
Fig. 4. TPD-CO2 analysis of the carbon catalysts.
3.2. Synthesis of N-substituted-gamma-lactams under
microwave irradiation
Under our experimental conditions basic catalysis and
microwave activation, 2-pyrrolidione reacts with 1-heptanal at
the N-position (Scheme 1). The mass spectrum of the reaction
product confirms that N-substituted-gamma-lactam of type B, N-
1-heptenyl-2-pyrrolidinone, is selectively obtained (MS m/s: 182
(M+), 125, 97, 87, 70, 57, 42). As we have shown previously, the
nature of the products in this reaction depends upon the choice of
the catalyst type. Alkaline-promoted carbons are appropriate mate-
rials to catalyze basic organic reactions showing basic sites with
strength up to pKa = 16.5 [29]. Considering that the NH group of
2-pyrrolidinone presents a pKa = 11.3 [10], these basic carbons are
appropriate catalysts to perform the N-substitution (Scheme 1).
The basicity probe reaction of Knoevenagel condensation
showed that most of the active sites in the alkaline promoted car-
bons have basic strength between 9 ≤ pKa ≤ 13.3 and a few of them
between 13.3 ≤ pKa ≤ 16.5 (Fig. 5).
40
35
30
25
20
15
10
5
1pKa=9
2pKa=10.7
3pKa=13.3
4pKa=16.5
0
Na
Cs
NaCs
1 Time reaction: 240min at 393K
2 Time reaction: 240min at 393K
3 Time reaction: 480min at 383K
4 Time reaction: 420min at 403K
Fig. 5. Catalytic activity measurements of the activated carbon-supported catalysts obtained by Knoevenagel basicity test reaction of benzaldehyde with methylenic com-
pounds (1:1) (ethyl cyanoacetate, pKa = 9, 240 min at 393 K; ethyl acetoacetate, pKa = 10.7, 240 min at 393 K; diethyl malonate, pKa = 13.3, 480 min at 383 K; ethyl bromoacetate,
pKa = 16.5, 420 min at 403 K).

V. Calvino-Casilda et al. / Applied Catalysis A: General 398 (2011) 73–81
79
Table 4
Kinetic constants for the C N coupling reaction of 2-pyrrolidinone with 1-heptanal assisted by microwave irradiation (600 W, 5 min) using basic carbon catalysts.
Catalyst
Power (W)
T (K)
k (× 102 M−1 s−1 g−1
)
k (× 105 M−1 s−1 m−2
)
cat
Norit
600
600
600
600
a381–388
a381–388
a381–388
a381–388
0.36
19.4
21.2
17.2
0.25
13.9
15.5
12.2
Na-Norit
Cs-Norit
NaCs-Norit
[2-pyrrolidinone]t = 0 = 7 M; [1-heptanal]t = 0 = 7 M.
a
Reaction time: 5 min at 600 W.
3.2.1. Kinetic study
and 1500 rpm). Under these reaction conditions, no considerable
change in catalytic activity was detected.
Scheme
1
shows the carbon–nitrogen coupling of 2-
pyrrolidinone and 1-heptanal. It is supposed that the basic
carbon catalyst abstract the proton of the NH group from the
lactamic ring (pKa = 11.3 [10]). Then, the C N coupling is pro-
duced by the nucleophilic attack of the lactamic anion to the
carbonyl group of the aldehyde forming the adduct A. However,
the adduct (A) formed here is unstable and it is stabilized by losing
a water molecule leading to the final product, N-1-heptenyl-2-
pyrrolidinone (B). The reaction proceeds with 100% selectivity
to N-1-heptenyl-2-pyrrolidinone under all reaction conditions.
The reported selectivity was determined in the following way
[yield of desired product]/([yield of detected product] + [detected
reactant]). The total balance calculated to carbon atoms was in all
cases better than 98%.
3.2.2. Influence of alkali promoter in the supported catalysts
The influence of the metal supported on the catalyst was studied
for the reaction between 2-pyrrolidinone and 1-heptanal where it
was evident that the activity in reaction of the pristine Norit carbon
increased once it was impregnated with the corresponding alkali
salts (Table 5). The results obtained showed the following order
in activity: Norit < NaCs-Norit < Na-Norit < Cs-Norit. Thus, conver-
sions of 72% and 100% selectivity are reached in only 5 min of
reaction when Cs-Norit is the catalyst. Closer conversions (around
69% and 100% selectivity for Na-Norit and 64% and 100% selectivity
for NaCs-Norit) are obtained when the catalyst is doped with Na.
It is expected that the basic properties of carbon catalysts have
Considering that the reaction is equimolar, the integrated rate
expressions for the proposed first and second order kinetic models
were simplified as shown next:
a particular influence on the activity and selectivity of the C
N
coupling reaction. The thermogravimetric analysis data showed
in Table 2 indicate that the metal content diminishes when the
size of the alkaline cation increase as a consequence of the greater
difficulty in accessing inside the pores in case of cesium than in
case of sodium. In addition, the XPS results showed slight cesium
enrichment at the surface while sodium was not detected at the
surface. Cs-Norit sample exhibited higher activity in the reaction
than the rest of samples indicating the better effectiveness as cata-
lyst. Kinetic studies of the reaction confirm the proposed theory and
Cs-Norit showed the highest values of kinetic rate constants. These
results clearly show that basic strength of active site play dominant
role in this reaction. This is clearly valid under both thermal as well
as microwave conditions.
First order; r = k[2-pirrolidinona]
ln[A] = − k(t) + ln[A0]; ln[A0(1 − x)] = −k(t) + ln[A0]
Second order; r = k[2-pirrolidinona][1-heptanal]
1/[A] = k(t) + 1/[A0]; 1/[A0(1 − x)] = k(t) + 1/[A0]
where [A0] is the initial concentration of 2-pyrrolidinone, x repre-
sents the conversion of the product B, A0(1 − x) is the concentration
of 2-pyrrolidinone which has not reacted, and t is the reaction
time. A first order or exponential kinetic would fit the experimen-
tal data ln [2-pyrrolidinone] versus time to a line with slope k,
while a second order or hyperbolic kinetic would fit the experimen-
tal data 1/[2-pyrrolidinone] versus time to a line with slope k. In
this case, for the equimolecular reaction between 2-pyrrolidinone
and 1-heptanal, a higher linear correlation coefficient was obtained
when representing ln [reactant] versus time, confirming that the
proposed reaction followed a first order kinetic where the rate
determining step of the reaction was the abstraction of the proton
by the basic carbon. Table 4 shows the kinetic constants calculated
for the different catalysts. From these results it can be said that the
rate constants decrease in the order: Cs-Norit > Na-Norit > NaCs-
Norit > Norit.
3.2.3. Other examples of microwave assisted synthesis of
N-substituted-gamma-lactams over alkali carbon catalysts
We also study the synthesis of other N-substituted-gamma-
lactams by using 2-pyrrolidinone and 2-indolinone as gamma-
lactams, and 1-heptanal and 1-octanal as substituent agents. To
carry out the reactions an equimolar mixture (2 mmol) of the
reactants and Cs-Norit catalyst (10 wt%) was irradiated under
microwaves at 600 W for 5 min. When 2-pyrrolidinone and 1-
octanal were employed yields of 49% were reached versus 72%
obtained when 1-heptanal was used as substituent agent. The use
of 2-indolinone as gamma-lactam and 1-heptanal as aldehyde,
decreases the final conversion values up to 36% due to the major
steric impediment as occurs in the reaction between 2-indolinone
and 1-octanal where yields of 28% were reached.
Under our experimental conditions, the reaction was neither
controlled by external nor internal diffusion. This experiment
was carried out by using different particle sizes of the catalysts
(0.074, 0.140 and 0.250 mm) and different stirring rates (600
Table 5
Carbon–nitrogen coupling reaction between 2-pyrrolidinone and 1-heptanal under microwave activation in presence of alkali-Norit catalysts (t = 5 min at 600 W).
Catalyst
Noritb
1.7
Na-Noritb
68.8
Cs-Noritb
72.0
NaCs-Noritb
64.4
Conversion (%)a
t = 5 min, 600 W
Equimolar amount of 2-pyrrolidinone and 1-heptanal (2 mmol).
a
Amount of catalyst: 0.02 g.
100% selectivity to N-1-heptenyl-2-pyrrolidinone.
b

80
V. Calvino-Casilda et al. / Applied Catalysis A: General 398 (2011) 73–81
Table 6
TOF for carbon–nitrogen coupling reaction between 2-pyrrolidinone and 1-heptanal
under microwave (600 W, 5 min) and conventional thermal (373 and 393 K, 1 h)
activation in presence of alkali-Norit catalysts.
TOF (s−1
)
Catalyst
Na-Norit
Cs-Norit
NaCs-Norit
MW (381–388 K)a
Batch (373 K)b
Batch (393 K)b
0.029
0.006
0.014
2.40
0.108
0.153
0.358
0.013
0.025
a
600 W, t = 5 min.
t = 1 h.
b
Knoevenagel probe reaction results demonstrated that carbon
catalysts contain basic sites strong enough to perform the N C cou-
pling reaction between 2-pyrrolidinone and 1-heptanal. Table 6
presents TOF data for the studied reaction. The results in this table
show that Cs-Norit catalyst displays the highest TOF value under
microwave and conventional thermal activation than Na-Norit and
NaCs-Norit catalysts. This suggests that Cs-Norit is basic enough to
carry out the reaction proving to be the most effective catalyst.
Fig. 6. Microwave activation versus conventional thermal activation (batch) in the
N-substitution of 2-pyrrolidinone with 1-heptanal catalyzed by basic carbons.
3.2.4. Microwave activation versus conventional thermal
activation
The reaction carried out under conventional thermal activation
in a batch reactor when using equimolar amounts of reactants
was negligible. Therefore, the reaction between 2-pyrrolidinone
and 1-heptanal was carried out using an excess of the aldehyde
(1-heptanal, 7.00 mmol) at temperatures of 373 and 393 K over Na-
Norit, Cs-Norit and NaCs-Norit catalysts. The excess of 1-heptanal
not used during reaction was filtered and then recycled.
Fig. 6 shows conversions obtained at 373 and 393 K in 4 h in a
batch reactor. From these results it can be concluded that under
conventional thermal activation (batch) all carbon catalysts were
active in the C N coupling reaction between 2-pyrrolidinone and
1-heptanal using an excess of aldehyde. An increase in the reaction
temperature resulted in an increase of the conversion maintaining
the selectivity (100%) to N-1-heptenyl-2-pyrrolidinone.
Fig. 6 also compared the results obtained under conven-
tional thermal activation (373–393 K) with those obtained under
microwave activation in a close range of temperatures (381–388 K).
These results proves how efficient is microwave activation (5 min,
60 < conversion(%) < 70, 100% selectivity) versus conventional ther-
mal activation (1 h, 30 < conversion(%) < 50, 100% selectivity).
Anyway, our basic carbons under microwave activation turned out
suitable catalysts to carry out the proposed reaction in very short
times and under mild conditions being also able to be reused in four
cycles of reaction without significant changes in the final yield of
the reaction (Fig. 7).
4. Conclusions
The effect of microwaves in the activation of alkaline promoted
carbons has been explored in the N-substitution of 2-pyrrolidinone
with 1-heptanal to obtain N-substituted-gamma-lactams for the
synthesis of important neuroexcitatory pharmaceuticals. Enhance-
ment effect on the reaction rate by combining the basicity of the
carbon catalysts and microwaves is presented as an alternative
method for the selective construction of C N bonds in the synthesis
of N-1-heptenyl-2-pyrrolidinone derivatives. It was also found that
there is a substantial enhancing effect in the yield when microwave
irradiation was used to activate the reaction instead of the con-
ventional thermal activation methods. This process can be also
generalized for the production of similar fine chemicals due to the
mild conditions that this system offers. In addition, although a large
body of work dealing with microwaves activation, only a relatively
small number of papers report the influence of the reaction condi-
tions on the rate and yields of chemical reactions. It is important
that those parameters are fine tuned and controlled to maximize
the microwave effects. We have found that among all the experi-
mental procedures induced by heterogeneous media employed for
the synthesis of numerous chemical compounds, the combination
of microwave irradiation with alkaline carbons offers interesting
prospects because excellent yields can be achieved under very mild
conditions.
100
Acknowledgements
90
80
70
60
50
40
30
20
10
0
Cs-Norit
V. Calvino-Casilda thanks CSIC for a postdoctoral contract (JAE-
Doc). Norit pristine carbon has been kindly supplied by Norit
Company. This work has been supported by Spanish Minister of Sci-
ence and Innovation (project CTQ2010-18652). Authors thank Prof.
JLG. Fierro for XPS data. V. Calvino-Casilda thanks F. Rosa-Vivas for
his great support.
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