SnCl2-catalyzed synthesis of carbamates from renewable origin alcohols

Article abstract of DOI:10.1007/s11696-017-0349-7

Effects of structure and reactivity of renewable origin alcohols in the conversion and selectivity of the SnCl₂-catalyzed reactions in the presence and absence of urea were assessed. Convenient simple and suitable method for the synthesis of carbamates from renewable origin alcohols and urea in one-step are provided. We have assessed the activity of SnCl₂ catalyst, a commercially affordable Lewis acid, in reactions of urea alcoholysis with different natural origin alcohols (geranyl, neryl, bornyl, cinnamyl, α-terpinyl and benzyl alcohols), aiming to synthesize carbamates, which are biologically active compounds, building blocks in organic synthesis and raw material to synthesize polyurethanes. The low cost of urea, the water tolerant catalyst and phosgene free reaction are positive aspects of this carbamates synthesis process. The different reaction pathways were assessed. A mechanism was proposed based on FT-IR experiments and experimental data.

Full text of DOI:10.1007/s11696-017-0349-7

Chemical Papers
https://doi.org/10.1007/s11696-017-0349-7
ORIGINAL PAPER
SnCl2‑catalyzed synthesis of carbamates from renewable origin
alcohols
Márcio José da Silva1 · Diego Morais Chaves1
Received: 12 September 2017 / Accepted: 21 November 2017
© Institute of Chemistry, Slovak Academy of Sciences 2017
Abstract
Efects of structure and reactivity of renewable origin alcohols in the conversion and selectivity of the SnCl2-catalyzed
reactions in the presence and absence of urea were assessed. Convenient simple and suitable method for the synthesis of
carbamates from renewable origin alcohols and urea in one-step are provided. We have assessed the activity of SnCl2 catalyst,
a commercially afordable Lewis acid, in reactions of urea alcoholysis with diferent natural origin alcohols (geranyl, neryl,
bornyl, cinnamyl, α-terpinyl and benzyl alcohols), aiming to synthesize carbamates, which are biologically active compounds,
building blocks in organic synthesis and raw material to synthesize polyurethanes. The low cost of urea, the water tolerant
catalyst and phosgene free reaction are positive aspects of this carbamates synthesis process. The diferent reaction pathways
were assessed. A mechanism was proposed based on FT-IR experiments and experimental data.
Keywords Tin(II) catalysts · Carbamates · Terpenic alcohols · Phosgene free process
Introduction
In special, the synthesis of renewable origin alcohol
derivative carbamates can provide compounds with potential
biological activity, as acetyl cholinesterase inhibitors, result-
ing in the development of eco compatible and potentially
safe pesticides (Martino et al. 2010; Berg et al. 2011).
There are diferent methods to synthesize carbamates,
some of them in large-scale processes. Carafa and Quar-
anta reported a review where several alternative processes,
some of them based on carbon dioxide, an environmentally
benign reactant, were carefully described (Carafa and Quar-
anta 2009). Others synthesis routes involving amination,
transesterifcation or reactions with isocyanates were also
reported (Baba et al. 2002; Fukuoka et al. 1984; Salvatore
et al. 2001). However, such reactions involve drastic condi-
tions (i.e., high temperatures) and are multi-step processes.
Consequently, synthetic methods under milder conditions
have since been investigated. For instance, Feroci et al. syn-
thesized carbamates via a cyanomethyl anion/carbon dioxide
system (Feroci et al. 2003).
Organic carbamates have been presenting extensive util-
ity in many areas of organic synthesis as pharmaceuticals
intermediates, for the protection of amino groups in peptide
chemistry and linkers in combinatorial chemistry (Yu and
Huiyuan 2002; Ray and Chaturvedi 2004; Ray et al. 2005).
In addition, carbamates may be converted to isocyanates,
which are starting materials for polyurethanes production
(Rios et al. 2013). Traditionally, organic carbamates are pro-
duced in large scale using harmful reagents like phosgene
(Chaturvedi et al. 2007). However, due to the high toxicity
of phosgene and the generation of HCl as a byproduct, the
developing of environmental friendly processes to synthe-
size carbamates has become interesting from the synthetic
and environmental viewpoint (Baba et al. 2005).
Due to environmental reasons, the use of urea to syn-
thesize carbamates has been widely explored (Shimizu and
Sodoeka 2007). Chaudhari et al. synthesized carbamates
through reactions of substituted urea with alcohols using
diferent metal oxides as catalysts, among which, the n-butyl
tin oxide (Chaudhari et al. 2004). Wang and co-workers have
reported the synthesis of methyl N-phenyl carbamate using
Electronic supplementary material The online version of this
article (https://doi.org/10.1007/s11696-017-0349-7) contains
supplementary material, which is available to authorized users.
* Márcio José da Silva
silvamj2003@ufv.br
1
Chemistry Department, Federal University of Viçosa,
Viçosa, Minas Gerais 36570-000, Brazil
Vol.:(0123456789)
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phenyl urea and methanol as starting materials (Wang et al.
2004, 2008).
α-terpinyl (> ca. 96 wt%) alcohols] were acquired from
Sigma-Aldrich, as well as the anhydrous tin(II) chloride
(ca. 99.9 wt%). Urea was GE (99.5 wt%). Benzyl and cin-
namyl alcohols (ca. 99 wt%) were too purchased from
Sigma-Aldrich.
Because of the detrimental corrosive efects of Brønsted
acids, Lewis acid catalysts became a viable option, and
its uses have since exponentially increased in the fne and
bulk chemical industries during the last couple of decades
(Corma and Garcia 2003). Nonetheless, essential aspects
such as the high cost, laborious manipulation and the low
water tolerance of Lewis acid traditionally used in organic
synthesis (i.e., BF3, SnCl4) have hampered its use at indus-
trial scale (Lotero et al. 2005).
SnCl2‑catalyzed urea alcoholysis reactions
with renewable origin alcohols
In all the catalytic tests performed in a 50 mL three-necked
glass flask, equipped with sampling system—a reflux
condenser—in thermostatic bath with magnetic stirrer, a
large excess of urea to shift the equilibrium towards the
carbamates formation was employed. Typically, alcohol
(2.375 mmol) and urea (47.500 mmol) were dissolved in
DMSO (15 mL solution) at 1:20 molar ratio. Airfow was
used to remove the ammonia from the reactor. The solution
was stirred, heated to reaction temperature (ca. 413 K) and
SnCl2 catalyst was then added (15 mol%), starting the reac-
tion. The naphthalene was the internal standard. In almost
runs, airfow was generated by a small air pump and led
by silicone hose to the reactor, aiming the removal of NH3
produced in the reaction.
Recently, we have explored the combination of urea and
β-citronellol to synthesize β-citronellyl carbamate from
tin(II)-catalyzed reactions (Da Silva and Morais 2016). Due
to their molluscicidal efect, analogous carbamates such as
N-methyl terpinyl carbamates are used as biologically active
compounds (Radwan and El-Zemity 2001; El-Zemity 2006).
Inspired by these fndings, we have extended the scope of
SnCl2-catalyzed urea alcoholysis reactions to others alcohols
from biomass, which is a renewable source for the produc-
tion of monoterpene and aromatic derivatives, attractive
platform-molecules to synthesize a plethora of chemicals
(Zakzeski et al. 2010).
Tin(II) halides are easily handle, water tolerant, inexpen-
sive and solid Lewis acids, and have successfully catalyzed
reactions to convert renewable feedstock such as FFA and
glycerol to esters and solketal, respectively (Cardoso et al.
2009; Goncalves et al. 2011; Da Silva et al. 2011). In addi-
tion, though being used in homogeneous phase, tin catalysts
can be reusable and are less corrosive than mineral acids (Da
Silva et al. 2015; Cardoso et al. 2008).
Reaction monitoring
We followed the reaction progress by taking aliquots at regu-
lar intervals and analyzing them via gas chromatography
[GC Varian 450, FID, ftted with RTX®-5 capillary column
(0.25 μm × 0.25 mm × 30 m)]. The temperature program
was as follows: 80 °C/3 min, 10 °C/min up to 230 °C. Both
injector and detector were kept at 250 °C temperature. Was
used H2 as carrier gas at 1.5 mL/s. The reaction yields were
calculated by matching the areas of the carbamates GC
peaks into the corresponding calibration curves.
In this work, we have wished to explore the pathway of
SnCl2-catalyzed reactions of diferent renewable origin alco-
hols with urea. Previously, when applied to the β-citronellol,
this procedure showed signifcant advantages over Brønsted
acids as well as other Lewis acid catalysts (Da Silva and
Morais 2016). Herein, the scope of the process was extended
to various renewable origin alcohols. The main products of
the reactions were isolated and characterized. Monitoring
of pH value during the reactions, besides FT-IR and NMR
spectroscopies analyses provided signifcant information that
allowed doing insights on reaction mechanisms of carba-
moylation, dehydration and oligomerization.
Identifcation of the reaction products
Reaction products were identifed by analyses carried out
on a Shimadzu GC2010 Plus gas chromatograph cou-
pled with a GCMS-QP2010 Ultra mass spectrometer
(Tokyo, Japan) with a RTX®-5-Wax capillary column
(0.25 μm × 0.25 mm × 30 m) and He as the carrier gas at
2 mL/min. The temperature profle was as follows: 80 °C
for 3 min, 10 °C/min up to 220 °C. The GC injector and
MS ion source temperatures were kept at 240 and 250 °C,
respectively. The MS detector was operated in the EI mode
at 70 eV, with a scanning range of m/z 50–400. The spec-
troscopic data of products are in electronic supplementary
material (ESM).
Materials and methods
Chemicals
All chemicals and solvents were purchased from commer-
cial sources and used as received. All terpenic alcohols
[β-citronellyl (ca. 99 wt%), bornyl (ca. 97 wt%), geranyl
(ca. 98 wt%), neryl (ca. 97 wt%), linalyl (ca. 97 wt%) and
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reactions. So, in this work we verifed this efect by per-
forming the reactions at the same conditions previously
optimized by us when we investigated the efciency of
Sn(II) catalysts in the urea alcoholysis reaction with
β-citronellol (Da Silva and Morais 2016). The kinetic
curves obtained in the presence and absence of are SnCl2
catalyst follows as displayed in Fig. 1a, b, respectively.
With the exception of the reactions with geranyl and
neryl alcohols, the presence of SnCl2 catalyst noticeably
improved the conversions for either allylic alcohols (i.e.,
neryl, geranyl and linalyl alcohols), cyclic alcohols (i.e.,
terpinyl and bornyl alcohols) and primary alcohols (i.e.,
cinnamyl and benzyl alcohols).
Measurements of pH values
To verify the possible presence of Brønsted acids in the reac-
tion, pH measurements were carried of solutions contain-
ing diferent compositions. The electrode potential variation
was measured with a potentiometer (Bel instrument, model
W3B, glass electrode).
Results and discussion
General aspects
The hydroxyl group nature was a key-aspect to gov-
ern the reactivity of diferent alcohols in the presence of
urea. In SnCl2-catalyzed reactions, the allylic secondary
alcohols were the most reactive (i.e., neryl and geranyl
alcohols), whereas the tertiary alcohols (i.e., α-terpinyl
and linalyl alcohols) were the less reactive. Although the
conversions have been signifcantly lower, the same was
observed in the blank-reactions.
In a previous work, we selected the SnCl2 as more active
tin(II) catalyst for alcoholysis reactions of urea with
β-citronellol (Da Silva and Morais 2016). In that work,
413 K was the temperature more adequate, while the optima
molar ratio between urea and alcohol was 1:20. The solvent
DMSO was also important for the carbamate selectivity,
because reduced the concurrent reactions (i.e., oligomeriza-
tion, dehydration), which were dominant when it was absent.
These optimized reaction conditions were applied
to assess the behavior of other natural origin alcohols in
SnCl2-catalyzed reactions in the presence and absence of
urea.
Although the urea has been used in excess (ca. 1:20
in relation to the alcohol), it was not enough to convert
the alcohols to carbamate at 413 K temperature. Indeed,
the presence of SnCl2 was enough essential for the car-
bamoylation reaction of alcohols occurs with high carba-
mates selectivity. For instance, whilst in the absence of
catalyst only ca. 19% of selectivity was achieved for gera-
nyl carbamate, in the SnCl2-catalyzed reactions a selectiv-
ity of ca. 97% was obtained (Fig. 2a, b).
Urea alcoholysis with renewable origin alcohols:
efects of substrate nature
The structure of the alcohol substrate can play a pivotal
role for the success of tin-catalyzed urea alcoholysis
benzylic alcohol
geraniol
60
50
40
30
20
10
0
60
geraniol
nerol
60
50
nerol
50
borneol
40
borneol
linalool
terpineol
benzyl alcohol
40
30
terpineol
cynamol
cynamol
30
20
linalool
80
20
10
10
0
0
20
40
60
100
120
0
20
40
60
80
100
120
0
time (min)
time (min)
(a)
(b)
Fig. 1 Kinetic curves of urea alcoholysis in the presence (a) and
absence (b) of SnCl2 catalyst in reactions without airfow. Reac-
tion conditions: alcohol (2.395 mmol); alcohol: urea molar ratio
(1:20); temperature (413 K); SnCl2 concentration (15 mol%); DMSO
(15 mL); naphthalene was the internal standard
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100
80
60
40
20
0
30
25
20
15
10
5
benzyl carbamate
benzyl carbamate
geranyl carbamate
neryl carbamate
neryl carbamate
geranyl carbamate
cinnamyl carbamate
cinnamyl carbamate
bornyl carbamate
linalyl and terpinyl carbamate
bornyl carbamate
0
linalyl and terpinyl carbamate
0
20
40
60
80
100
120
0
20
40
60
80
100
120
time (min)
time (min)
(b)
(a)
Fig. 2 Carbamate selectivity of urea alcoholysis in the presence
(a) and absence of SnCl2 catalyst (b) in reactions without airfow.
Reaction conditions: alcohol (2.395 mmol); urea (40.790 mmol);
alcohol:urea molar ratio (1:20); temperature (413 K); SnCl2 concen-
tration (15 mol%); DMSO (15 mL); naphthalene was the internal
standard
The nature of the substrate remarkably afected the
reaction selectivity as shown in Fig. 2. Linalyl and terpinyl
alcohols did not provide selectivity to carbamates either
in the absence or presence of SnCl2. Conversely, in the
reactions between geranyl or neryl alcohols with urea, high
carbamate selectivity (ca. 90%) was achieved in the pres-
ence of SnCl2. All the spectroscopic data of carbamates
are in electronic supplemental material (ESM).
When we have comparing the kinetic curves of reactions
with or without airfow we have found that benzyl, geranyl
and neryl alcohols remained as the more reactive substrate.
Although the conversions are remarkably higher for
SnCl2-catalyzed reactions under airfow (i.e., see Figs. 1,
3), the carbamate selectivity was only slightly enhanced,
mainly in the presence of catalyst. For instance, the selectiv-
ity for neryl and geranyl carbamates was close to ca. 90%
either in the absence or presence of airfow (Figs. 2a, 4a,
respectively).
Aromatic alcohols had a diferent behavior. Benzyl
alcohol was much more reactive than cinnamyl alco-
hol either in the presence or absence of tin(II) chloride
catalyst.
Urea alcoholysis with renewable origin alcohols:
efects of airfow on the total selectivity
of the reaction products in the presence
and absence of SnCl2 catalyst
Urea alcoholysis with renewable origin alcohols:
efects of airfow on the reactions of urea
alcoholysis with diferent alcohols
The biggest challenge for the reactions of urea alcoholysis
with terpenic alcohols at temperatures higher than 373 K is
the occurrence of undesirable competitive transformations
such as the dehydration of alcohols and oligomerization of
the olefns formed.
Urea alcoholysis reactions are reversible processes that gen-
erate ammonia as byproduct (Scheme 1).
Therefore, an efective strategy to increase the carbamate
yielding is the removal of side-product ammonia, which
should shift the equilibrium towards products. To do it, we
performed the reactions under airfow. The kinetic curves
are in Figs. 3.
In Figs. 5 and 6 we displayed data that illustrates how
the diferent alcohols behave in the reactions carried out at
413 K in the presence or absence of catalyst without airfow
(Fig. 5a, b, respectively) and under airfow (Fig. 6a, b).
Scheme 1 SnCl2-catalyzed urea
O
O
alcoholysis reaction
SnCl2
R
H
O
NH2
NH3
H2N
NH2
+
+
R
O
DMSO, 413 K
air flow
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100
80
60
40
20
0
nerol
benzylic alcohol
nerol
30
25
20
15
10
5
geraniol
benzyl alcohol
geraniol
cynamol
borneol
linalol
terpineol
linalool
cynamol
terpineol
borneol
0
0
15
30
45
60
75
90 105 120
0
15
30
45
60
75
90
105 120
time (min)
time (min)
(a)
(b)
Fig. 3 Kinetic curves of urea alcoholysis with diferent alcohols
in the presence (a) and absence of SnCl2 catalyst under airfow (b).
Reaction conditions: alcohol (2.395 mmol); urea (40.790 mmol);
alcohol: urea molar ratio (1:20); temperature (413 K); SnCl2 concen-
tration (15 mol%); DMSO (15 mL); airfow (15–20 mL/min); naph-
thalene was the internal standard
100
80
60
40
20
0
geranyl carbamate
neryl carbamate
benzyl carbamate
neryl carbamate
30
25
20
15
10
5
benzyl carbamate
geranyl carbamate
cinnamyl carbamate
bornyl carbamate
cinnamyl carbamate
bornyl carbamate
0
0
15
30
45
60
75
90 105 120
0
15
30
45
60
75
90 105 120
Time (min)
Time (min)
(a)
(b)
Fig. 4 Selectivity for carbamates in urea alcoholysis in the pres-
ence (a) and absence of SnCl2 catalyst (b) and with airfow. Reac-
tion conditions: alcohol (2.395 mmol); alcohol:urea (40.790 mmol);
urea molar ratio (1:20); temperature (413 K); SnCl2 concentration
(15 mol%); DMSO (15 mL); airfow (15–20 mL/min); naphthalene
was used as the internal standard
In most cases, the conversions of the reactions in the
presence or absence of SnCl2 were approximately the
same for both reactions without (Fig. 1a, b) or with airfow
(Fig. 3a, b). However, the selectivity of products for the
SnCl2-catalyzed reactions (Figs. 5a, 6a) were signifcantly
higher than those non-catalyzed (Figs. 5b, 6b).
higher than 90% in both reactions. Benzyl carbamate was
obtained with ca. 90 and 67% of selectivity in the reac-
tions without and with airfow, respectively. Conversely,
cinnamyl and bornyl alcohols were preferably converted
to oligomers at the same reaction conditions.
Naphthalene used as the standard could be lost due to
sublimation in the airfow. However, the naphthalene GC
peak area in the chromatograms remained constant during
Tin(II) chloride-catalyzed reactions achieved high car-
bamate selectivity either with or without airfow. Gera-
nyl and neryl carbamates were obtained with selectivity
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carbamates
carbamates
isomers
dehydration products
oligomers
isomers
80
70
60
50
40
30
20
10
0
dehydration products
oligomers
100
80
60
40
20
0
geraniol
nerol
cynamol benzylic
alcohol
borneol
geraniol
nerol
cynamol
benzylic
alcohol
borneol
(a) SnCl2-catalyzed reactions
(b) non-catalyzed reactions
Fig. 5 Product selectivity of urea alcoholysis in the presence (a) and
absence of SnCl2 catalyst (b) in reactions without airfow. Reaction
conditions: alcohol (2.395 mmol); urea (40.790 mmol); alcohol:urea
molar ratio (1:20); temperature (413 K); SnCl2 concentration
(15 mol%); DMSO (15 mL); reaction time (2 h); naphthalene was
used as the internal standard
carbamates
100
80
60
40
20
0
carbamates
isomers
dehydration products
oligomers
isomers
90
80
70
60
50
40
30
20
10
0
dehydration products
oligomers
geraniol
nerol
cynamol benzylic
alcohol
borneol
geraniol
nerol
cynamol
benzylic
alcohol
borneol
(a) SnCl2-catalyzed reactions
(b) non-catalyzed reactions
Fig. 6 Product(s) selectivity of urea alcoholysis in the pres-
ence or absence of SnCl2 catalyst (a, b, respectively) in reac-
tions under airfow. Reaction conditions: alcohol (2.395 mmol);
urea (40.790 mmol); alcohol: urea molar ratio (1:20); temperature
(413 K); SnCl2 concentration (15 mol%); DMSO (15 mL); airfow
(15–20 mL/min); reaction time (2 h)
kinetic monitoring. This was possible due to the use of the
system in refux.
consumed the substrate but did not provide the desired prod-
ucts (i.e., carbamates), compromising thus the selectivity.
Nonetheless, to assess the temperature efect, we per-
formed the reactions in absence of urea (Fig. 7). Linalool
and α-terpineol were excluded from the section because they
did not provide carbamates. The tertiary hydroxyl group of
these substrates is highly hindered and was very little reac-
tive for carbamoylation reaction.
Efect of temperature on conversion and selectivity
of SnCl2‑catalyzed renewable origin alcohols
reactions in the absence of urea
Monoterpenes when exposed to temperatures higher than
353 K may undergo undesirable reactions such as isomeri-
zation, dehydration and isomerization. These reactions
The reaction temperature favored the oligomerization
of all terpenic and aromatic alcohols (Fig. 7). In addition,
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dehydration products
isomerization products
autoxidation products
oligomerization products
75
60
45
30
15
0
75
60
45
30
15
0
geraniol
nerol
cynamol
borneol
benzyl alcohol
geraniol
nerol
cynamol borneol
benzylic alcohol
0
15
30
45
60
75
90
105 120
Time (min)
(a) conversion
a
(b) selectivity
Fig. 7 Conversion (a) and selectivity (b) of SnCl2-catalyzed reactions
without urea. Reaction conditions: alcohol (2.395 mmol); temperature
(413 K); SnCl2 concentration (15 mol%); DMSO (15 mL); reaction
δ-terpinolene, were formed from geraniol and nerol; camphene was
obtained from borneol; 4-methoxystyrene was formed from cinnamyl
alcohol; styrene from benzyl alcohol; isomerization products: mixture
of nerol and geraniol; autoxidation products: benzaldehyde and cinna-
maldehyde; oligomers: compounds with high molar weight determi-
nate via mass balance with use of naphthalene as the internal standard
a
time (2 h); naphthalene was the internal standard. Selectivity: The
reaction products were identifed through GC–MS analysis as fol-
lows: dehydration products: myrcene, limonene, o-cymene, α and
Scheme 2 Probable route of
oligomerization of geraniol
- H2O
H
O
and or H+
Oligomers
n
benzyl and cinnamyl alcohols were autoxidized to respective
aldehydes. The oligomerization can be reasonably explained
by the reaction depicted in the Scheme 2. Allylic alcohols
can undergo dehydration resulting in olefns, which can suf-
fer oligomerization in the studied reaction conditions (i.e.,
temperature 413 K, in the presence of Lewis and or Brønsted
acids).
Table 1 Measurements of acidity (pH values) of DMSO solutions
containing geraniol, SnCl2 and or urea
Entry
System
Measurement
of pH values
1
2
3
4
5
6
Pure DMSO
DMSO + SnCl2
Urea + DMSO
Urea + SnCl2 + DMSO
Geraniol + DMSO
Geraniol + SnCl2 + DMSO
6.0
5.9
8.0
5.8
7.0
4.0
Although high temperatures may be able to promote this
reaction, the presence of Brønsted acids in the solution also
could favor the substrates oligomerization. To verify the pos-
sible presence of Brønsted acids in the reaction, pH meas-
urements were carried out through the potential variation of
a glass electrode in a potentiometer and the main results are
presented in Table 1.
Conditions: DMSO solutions (5 mL); geraniol (9.58 mmol); urea
(9.58 mmol); SnCl2 catalyst (0.359 mmol; 7.5 mol%); temperature
(298 K)
The addition of SnCl2 to DMSO provoked only a slight
reduction of pH value (entries 1 and 2, Table 1). Conversely,
the measurements of acidity of the solutions DMSO with
alcohol containing SnCl2 catalyst showed that there was a
reduction of pH values after the addition of SnCl2 to the
solution. Indeed, the same fact occurred for other alcohols;
measurements of pH values of solutions containing other
alcohols were also performed, however, to simplify, only the
geraniol data were displayed.
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We have found that while the solution of SnCl2 in
DMSO shows pH value of 5.9, the pH of the DMSO solu-
tion containing the mixture SnCl2/geraniol was 4.0 (entries
2 and 6, Table 1). Therefore, hypothetic participation of
H+ cations as suggested by the Scheme 2 was unequivo-
cally confrmed.
conditions favored the substitution steps. Herein, the olefns
were preferentially formed.
The selectivity of dehydration products was determined
by GC–MS and 1H NMR analysis. In addition to dehydration
products, oligomers (ca. 50% of converted substrate) were
formed, and its calculation took place via mass balance of
reaction and using internal standard.
In addition, it is also possible that the Sn(II) cations may
too participate in the dehydration reaction, which results in
olefns that may undergo oligomerization under reaction
conditions. Experiments using stoichiometric amounts of
geraniol and SnCl2 were carried aiming the detection of tin-
alkoxide as well as the confrmation of the straight participa-
tion of Sn+2 cations in the dehydration reaction.
It is noteworthy that SnCl2 was used in large amount aim-
ing to detect the probable intermediate tin-alkoxide. None-
theless, the 13C NMR analysis performed at end of reaction
was unable to detect any change on the possible chemical
shift of carbon atom resonance signal linked to the atom
oxygen of geraniol. The chemical shift was ca. δ 58.3, before
or after of the reaction.
Initially, we tried to use 1H and 13C NMR spectroscopy
analyses to determine the reaction selectivity. It is requires
that products can be separate through silica column. How-
ever, it was not possible to isolate the products, due to its
similar polarity properties. So, the NMR spectrum analysis
of mixture was complicated due to the presence of multiples
resonance signals of olefns in a narrow range of chemical
shift. Alternatively, GC–MS analysis were performed after
2 h of reaction and allowed to quantify the products. The
Scheme 3 presents the dehydration products selectivity.
The ability of tin(II) chloride in eliminate hydroxide
group and generate carbenium ions was previously described
by Masuyama et al., which assessed reactions of substitu-
tion of propargyl alcohols with rich-electrons arenes and
amide (Masuyama et al. 2013). However, in that case, the
substrate structure, the presence of nucleophiles and reaction
On the other hand, the lowering of the pH value (Table 1)
can be attributed to the alkoxylation reaction of SnCl2 with
the alcohol (Scheme 4).
The reaction between geraniol and tin(II) chloride may
result on the release of H+ cations (i.e., HCl), which will be
responsible for the increase on medium acidity. This evi-
dence opened the way to studies of the possibility of alcoho-
lysis reaction proceeds via an alkoxide intermediate, which
we discuss in the next section.
The possibility of HCl released act as catalyst to produce
carbamate was assessed performing the urea alcoholysis
reaction with β-citronellol, either in the presence of hydro-
chloric acid alone and the SnCl2 catalyst (Table 2).
In the presence of HCl, the oligomers were the main
reaction products (ca. 87% selectivity) while citronellyl
H
Scheme 3 Selectivity for
dehydration products of
SnCl2-catalyzed reactions.
Reaction conditions: DMSO
(3 mL); temperature (413 K);
reaction time (2 h); without
airfow
H
H
H
H
myrcene
27 %
H
(Z)-ocymene
24 %
OH
(E)-ocymene
SnCl2
(100 mol %)
17 %
413 K, 2 h
geraniol
–terpinolene
10 %
α
limonene
22 %
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Chemical Papers
Scheme 4 Alkoxylation reac-
tion of SnCl2 with geraniol at
room temperature
OH
OSnCl
+ HCl
+
SnCl2
Table 2 Assessment the efect of HCl in the urea alcoholysis with
C-O
Cl-Sn
O-Sn
β-citronellol
C-H
OH
OH
C=C
CH
Run
Catalyst
Conversion Selectivity (%)
(%)
β-citronellyl
Oligomers
carbamate
geraniol + SnCl2
1
2
3
–
41
37
57
22
13
86
79
87
14
HCl
SnCl2
Geraniol
dried SnCl2
Reaction conditions: β-citronellol (2.395 mmol), urea (47.9 mmol),
2 h, 413 K, catalyst (15 mol%), DMSO (15 mL)
200
1050
1900
2950
4000
wavenumber (cm-1)
carbamate was the minority product (ca. 13% selectivity).
Conversely, in the SnCl2-catalyzed reaction the selectivity
of carbamate was noticeably higher than in the presence of
HCl catalyst (ca. 86 and 14%, respectively). It is sugges-
tive that indeed, the presence of SnCl2 plays a vital role on
alcoholysis reactions.
Fig. 8 FT-IR spectra of geraniol, SnCl2 and solution of thereof in
equimolar proportion. Conditions: The spectrum of solution contain-
ing geraniol and SnCl2 was recorded after 1 h of reaction to 333 K
was previously dried to a temperature of 363 K during 16 h
aiming the removal of hydration water. Nonetheless, as it
can be seen in Fig. 8, it was not possible to assure that all
the hydration water of the SnCl2 salt was totally removed.
So, although we have attributed the absorption bands at wave
number 356 cm−1 to Sn–O bond stretching, is possible that
they belong to hydrate tin(II) salt, whereas to the intermedi-
ate alkoxide.
Insights on mechanism of SnCl2‑catalyzed urea
alcoholysis reactions with renewable origin alcohols
Recently, we have performed measurements of FT-IR spec-
troscopy aiming to assess the mechanism of the reaction
of urea alcoholysis with β-citronellol (Da Silva and Morais
2016). In that case, FT-IR spectra of β-citronellol in the
presence of SnCl2 or urea have strong absorption bands
on the region of 350–550 cm−1, which are typically attrib-
uted to the Sn–O or Sn–N bond vibration bands (Nath et al.
2003). Although the Sn–O and Sn–N bond stretching bands
have been detected in the mixtures of SnCl2/β-citronellol
and SnCl2/urea, they were not detectable in the mixture of
SnCl2/β-citronellol/urea, due to the overlapping of absorp-
tion bands. To verify if the same will occur with geraniol,
(a) we ran a similar procedure and the results are displayed
in Fig. 8.
However, as in the previous work, we verifed via GC–MS
analysis that OCNH (i.e., isocyanic acid) was present in the
reaction aliquots (Da Silva and Morais 2016). Therefore, we
have proposed a mechanism involving an initial step where
thermal decomposition products of urea react with SnCl2
catalyst. A mechanism based on participation of isocyanic
acid is proposed to describing the SnCl2-catalyzed urea alco-
holysis reaction with geraniol (Scheme 1SP, ESM).
The role of Lewis acid catalyst in urea alcoholysis may
be coordinated to carbonyl group of urea to facilitate its
attack by hydroxyl group of alcohol. Aside, at 413 K tem-
peratures, the urea is thermally decomposed to ammonium
and isocyanic acid, an fact that explain the presence of
the isocyanic acid molecular ion in the GC–MS analysis
of aliquots collected at end of the reactions. Therefore, as
depicted in supplemental material (Scheme 1SP, ESM), the
The urea was not added because its solution infrared
radiation absorb in a broad range of wavenumber resulting
in an overlapping of absorption bands with ones of geran-
iol and SnCl2. Our intention was to detect the presence of
stretching bands of Sn–O bond, aiming assures that the
alkoxide intermediate was truly formed. To do it, the SnCl2
1 3

Chemical Papers
Scheme 5 Mechanistic proposal
for carbamoylation of terpenic
alcohols with urea
∆
CH2
CO(NH2)2
NH3 + NHCO
SnCl2 + ROH
R =
NH3 + NHCO
HCl
H3N
OR
HCl
Sn
H
ROH
Cl
N
C
O
H3N
Cl
Cl
O
C
Sn
HCNO
RO
NH2
H3N
OR
C
Sn
HCNO
O
Cl
N
H
OR
H3N
Cl
Cl
Sn
C
N
O
H
H
HCl
urea decomposition reaction provides isocyanic acid, which
will be a key-intermediate for the alcoholysis reaction.
Taking consideration of the facts above, it is reasonable
to suppose that on the frst step of the reaction, the SnCl2
catalyst sufers a ligands exchange reaction with isocyanic
acid providing an intermediate Sn(NCO)2 and releasing HCl.
The coordination of tin(II) to nitrogen atoms was recently
reported in literature by Fujita et al. (2013). Moreover, as
described by Zhao et al., this intermediate in solution, may
also be weakly coordinated to two urea molecules (Zhao
et al. 2009). We suppose that the alcohol may then shift the
coordinate ammonium generating an intermediate where the
alcohol molecule is coordinated to the tin.
very common in reactions involving nitrogen ligands and tin
catalysts (Fujita et al. 2013; Nath et al. 2003). Nonetheless,
oxygen ligands have adequate characteristics to coordinate
to the tin(II). So, in the Scheme 5, we explored another reac-
tion pathway where the tin-alkoxide intermediate is initially
formed via Sn–O bond. It is noteworthy highlight that low-
ering of pH value verifed throughout the SnCl2-catalyzed
alcoholysis reactions and FT-IR measurements reasonably
support this proposal.
In agreement with this proposal, after thermal decompo-
sition of urea, in the frst reaction step of catalytic cycle the
alkoxide is coordinated to the tin(II) catalyst through Sn–O
bond. A four-center intermediate is then generated by the
intramolecular nucleophilic attack of oxygen atom of alkox-
ide group to the coordinate isocyanic acid. This intermedi-
ate reacts with one HCl molecule generated in the reaction
between SnCl2 and alcohol (i.e., frst step of reaction). While
the chloride anion occupies the vacancy generated after the
intramolecular reaction between the alcohol molecule and
isocyanic acid both coordinate to the tin(II), the hydrogen
atom of HCl is bonded to the nitrogen atom of carbamoyl
group.
In the next step, occurs an intramolecular nucleophilic
attack of oxygen atom of alcohol hydroxyl group to the
carbonylic carbon atom of isocyanate anion, resulting in a
tin-carbamoyl intermediate. An ammonium molecule flls
the vacancy generated. So, this intermediate reacts with an
isocyanic acid molecule giving the alkyl carbamate product
and regenerating the tin(II) catalyst.
The crucial aspect of this proposed is the intermediate
initially formed. This intermediate is formed through Sn–N
bond. Literature have described that this coordination way is
1 3

Chemical Papers
Cardoso AL, Neves SCG, Da Silva MJ (2009) Kinetic study of alcoho-
lysis of the fatty acids catalyzed by tin chloride(II): an alternative
catalyst for biodiesel production. Energy Fuels 23:1718–1722.
https://doi.org/10.1021/ef800639h
The carbamate is then released in the next step and the
generated vacancy is flled by the isocyanic acid molecule,
regenerating the active catalytically specie, which is able to
react with another substrate molecule and restart the cata-
lytic cycle.
Chaturvedi D, Mishra N, Mishra V (2007) Various approaches for
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Conclusion
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neous to green homogeneous and heterogeneous catalysis. Chem
Rev 103:4307–4366. https://doi.org/10.1021/cr030680z
Da Silva MJ, Morais DC (2016) Tin-catalyzed urea alcoholysis with
β-citronellol: a simple and selective synthesis of carbamates. Catal
Lett 146:1517–1528. https://doi.org/10.1007/s10562-016-1769-7
Da Silva ML, Figueiredo AP, Cardoso AL, Natalino R, da Silva MJ
(2011) Efect of water on the ethanolysis of waste cooking soy-
bean oil using a tin(II) chloride catalyst. J Am Oil Chem Soc
88:1431–1437. https://doi.org/10.1007/s11746-011-1794-z
Da Silva MJ, Guimaraes MO, Julio AA (2015) A highly regioselective
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The carbon skeletal and hydroxyl group nature have played
an essential role over the conversion and selectivity of
SnCl2-catalyzed reactions between renewable origin alco-
hols and urea. The SnCl2 was an efcient catalyst to con-
verting allyl (i.e., geraniol and nerol) and primary alcohols
(benzyl or cinnamyl) to respective carbamates in urea alco-
holysis reactions, mainly under airfow. On the other hand,
no carbamate was obtained in the reactions with tertiary
alcohols (i.e., α-terpineol and linalool) and urea. The dif-
ferent reactivity of the alcohols was assessed at high tem-
peratures (ca. 413 K) also in the absence of urea. When in
the presence of urea, oligomers and dehydration products
were main products. Insights on reaction mechanisms were
done based on FT-IR and pH value measurements during the
reactions. The low cost of carbonylic reactant, and the usage
of a simple, less corrosive and inexpensive Lewis acid cata-
lyst, coupled with the non-use of phosgene are signifcant
breakthroughs of this method synthesis, which was highly
efcient for allylic and primary alcohols.
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jo0266036
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bonate from glycerol and urea using zinc-containing solid cata-
lysts: a homogeneous reaction. J Catal 297:137–141. https://doi.
org/10.1016/j.jcat.2012.10.001
Acknowledgements The authors are grateful to CNPq, CAPES, Rede
Mineira de Quimica and FAPEMIG for fnancial support.
Fukuoka S, Chono M, Kohno M (1984) A novel catalytic synthesis
of carbamates by the oxidative alkoxycarbonylation of amines in
the presence of platinum group metal and alkali metal halide or
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