Group 3 metal (Sc, La) triflates as catalysts for the carbomethoxylation of aliphatic amines with dimethylcarbonate under mild conditions

Article abstract of DOI:10.1016/j.tet.2003.12.020

The activity of Sc(OTf)₃ and La(OTf)₃ (OTf=SO ₃CF₃) as catalysts for the phosgene-free synthesis of carbamate esters via carbomethoxylation of aliphatic amines with dimethylcarbonate (DMC) has been investigated. In the presence of M(OTf) ₃ (M=Sc, La), primary and secondary aliphatic amines easily react with dimethylcarbonate, under very mild conditions (20°C), to afford carbamate esters with good yield and excellent selectivity (?100%). Sc(OTf)₃ is a more effective catalyst than the homologue La salt. The carbomethoxylation reaction requires as strict anhydrous conditions, as, at 20°C, the presence of water inhibits markedly the catalytic activity of both triflate salts. Temperature influences carbamate selectivity, which is lower at higher temperature because of deleterious formation of N-methylation side-products.

Full text of DOI:10.1016/j.tet.2003.12.020

Tetrahedron 60 (2004) 1531–1539
Group 3 metal (Sc, La) triflates as catalysts for the
carbomethoxylation of aliphatic amines with dimethylcarbonate
under mild conditions
a
Monica Distaso and Eugenio Quaranta
a,b,*
a
Dipartimento di Chimica, Campus Universitario, Universit a` di Bari, 70126 Bari, Italy
ICCOM-CNR, Dipartimento di Chimica, Campus Universitario, 70126 Bari, Italy
b
Received 10 September 2003; revised 12 November 2003; accepted 4 December 2003
Abstract—The activity of Sc(OTf)
3
and La(OTf)
3
(OTf¼SO
3 3
CF ) as catalysts for the phosgene-free synthesis of carbamate esters via
carbomethoxylation of aliphatic amines with dimethylcarbonate (DMC) has been investigated. In the presence of M(OTf) (M¼Sc, La),
3
primary and secondary aliphatic amines easily react with dimethylcarbonate, under very mild conditions (20 8C), to afford carbamate esters
with good yield and excellent selectivity (h 100%). Sc(OTf)
3
is a more effective catalyst than the homologue La salt. The
carbomethoxylation reaction requires as strict anhydrous conditions, as, at 20 8C, the presence of water inhibits markedly the catalytic
activity of both triflate salts. Temperature influences carbamate selectivity, which is lower at higher temperature because of deleterious
formation of N-methylation side-products.
q 2004 Elsevier Ltd. All rights reserved.
7
1
. Introduction
synthesis of organic carbonates have been implemented.
8
Aliphatic amines easily react with diphenylcarbonate, or
other organic carbonates having fairly good leaving
The search for new synthetic methods that minimize energy
requirements and reduce or eliminate the utilization of
hazardous reagents is a major target for ‘Green Chemistry’.
Much effort is currently being focussed on replacing
phosgene, which, because of its toxicity, is being less and
less employed in chemical industry as a starting material for
the synthesis of a number of chemicals, such as carbamates,
6
,9
groups. However, carboalkoxylation of aliphatic amines
by unactivated organic carbonates, such as dialkylcarbo-
1
0
needs a suitable catalyst in order to observe satisfactory
00
nates (Eq. 1; R¼alkyl; R ¼H, alkyl; R ¼alkyl), usually
2
1
0–13
conversion rate and selectivity. We have demonstrated
that CO itself is an effective catalyst for the synthesis
2
3
ureas, isocyanates and organic carbonates.
Cat:
0
00
0
00
00
RR NH þ ðR OÞ CO ! RR NCðOÞOR þ R OH
ð1Þ
of N-alkyl methylcarbamates from aliphatic primary amines
2
We have shown that carbon dioxide can be an effective
substitute for phosgene in the synthesis of carbamate esters
2
,12
0
00
0
00
2
and dimethylcarbonate (DMC).
metal catalysts have been more usually used to this end.
However, Lewis acid
0,13
RR NHC(O)OR (R¼alkyl, aryl; R ¼H, alkyl; R ¼alkyl).
1
These compounds are largely used as pharmaceuticals and
agrochemicals and also play a key role as intermediates in
chemical industry for the production of fine and commodity
A few of them have been studied as catalysts for the
1
0,13,14
carbamation of aromatic amines.
Such processes
0
catalysed both by organo-phosphorous Br o¨ nsted acids
00
4
(Eq. 1; R¼aryl; R ¼H, alkyl, aryl; R ¼alkyl or aryl) can be
chemicals. The development of phosgene-free routes to
carbamates is an important synthetic task and several other
approaches, based, for example, on the use of either CO or
6
carbonic acid diesters, are currently under study.
2
,8,15
1
6
5
and organic or inorganic bases. In most cases, quite severe
experimental conditions, such as high temperatures
.90 8C), are required, which often promote the formation
(
of undesired by-products, such as ureas and/or N-alkylation
products, lowering the selectivity to give the carbamate.
Aminolysis of organic carbonates has gained growing
attention as an alternative clean route to carbamate esters
in the last few years. This is favoured by the fact that
innovative phosgene-free methodologies for the industrial
2
Despite the number of metal systems investigated, so far the
behaviour of early transition metal derivatives and, more
0
specifically, d transition metal systems as catalysts in the
aminolysis reaction of unactivated carbonic acid diesters
Keywords: Carbamate esters; Scandium triflate; Lanthanum triflate;
Dimethylcarbonate; Amines.
1
3
*
Tel./fax: þ39-080-544-20-83;
still remains very poorly documented. To date, no report
has ever described the activity of Group 3 metal salts as
e-mail address: quaranta@chimica.uniba.it
0040–4020/$ - see front matter q 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2003.12.020

1
532
M. Distaso, E. Quaranta / Tetrahedron 60 (2004) 1531–1539
2 2
Table 2. Carbomethoxylation of PhCH NH with DMC in the presence of
catalysts for this particular purpose. As a continuation to our
2
,15
M(OTf) (M¼La, Sc) at ambient temperature (20 8C): influence of H O on
previous studies,
we have therefore focused our attention
3
2
a
the catalytic activity of the triflate salts
on the use of Group 3 metal triflates M(OTf) (M¼Sc, La;
3
OTf¼SO CF ) as potential catalysts for amine carbo-
3
3
Entry
Metal salt
M (La, Sc) (mmol)
Time
(h)
Carbamate
b
yield (%)
methoxylation. We have investigated the catalytic activity
of these salts at ambient temperature (20 8C), because of
the current widespread interest for new synthetic protocols
1
2
3
4
La(OTf)
La(OTf)
3
0.067
0.065
0.072
0.079
24.0
9.5
20.9
24
71
7
75
10
c
1
3
2
/H O
requiring mild experimental conditions, scarcely investi-
Sc(OTf)
Sc(OTf)
3
gated so far. In the last few years, Group 3 metal triflates
and, more generally, rare-earth metal (Ln) triflates have
been receiving great attention for their ability to promote a
wide variety of organic reactions selectively, under not
severe conditions. Interestingly, they have been shown to
exhibit excellent catalytic properties even in the presence of
Lewis bases containing N, O, P, S donor atoms.
d
3
2
/H O
a
2 2
PhCH NH : 0.100 mL, 0.916 mmol; DMC: 1.0 mL, 11.87 mmol (in all
the runs).
b
c
GC-yield versus the amine (internal standard: n-undecane (30 mL)).
O (8 mL; mol H
O/mol La¼7:1) was added to the suspension of the
salt in DMC before adding the amine.
1
7
H
2
2
d
H
2
O (8.5 mL; mol H O/mol Sc¼6:1) was added to the DMC solution of
2
the salt before adding the amine.
Herein, we describe, for the first time, the activity of both
Sc(OTf) and La(OTf) as catalysts for carbomethoxylation
of primary and secondary aliphatic amines with DMC and
document a few examples of utilization of these salts as
effective catalysts for the selective synthesis of carbamate
esters via aminolysis of DMC at ambient temperature.
3
3
other donor species (amine, OTf anion, DMC itself, etc.) for
the coordination sites on the metal centre and, therefore, can
inhibit the activation of the substrate (DMC). Anhydrous
conditions are required also to prevent the precipitation of
poorly soluble metal-carbamato-species (see Section 4.2),
which can easily form as a result of DMC hydrolysis in the
presence of the amine.
2
. Results and discussion
Table 3 summarizes the results obtained when linear or
2.1. Carbomethoxylation of aliphatic primary amines
with DMC promoted by M(OTf) (M5Sc, La) salts
branched aliphatic primary amines RNH (R¼benzyl, n-
2
3
butyl, allyl, iso-butyl) were reacted with DMC at 20 8C, at a
DMC/amine molar ratio close to 13:1, in the absence of any
catalyst (entries 3, 6, 9, and 12, Table 3) or in the presence of
catalytic amounts of M(OTf) (7–8% (mol/mol) vs RNH ;
Table 1 compares the behaviour of a few Group 3 metal
(Sc, La) salts as catalysts for the carbomethoxylation of
benzylamine with anhydrous DMC, at 20 8C. Anhydrous
3
2
M¼Sc or La). The triflate salts M(OTf) smoothly promote
3
LaCl , or hydrated La salts, such as LaCl ·7H O and
2
the carbomethoxylation of the investigated amines which
are converted into the corresponding carbamate esters in
good yield (Table 3).
3
3
La(NO ) ·7H O, show no or poor catalytic activity (entries
3
3
2
1
8
2
reaction conditions, both La(OTf) and Sc(OTf) effectively
–4, Table 1). Conversely, under otherwise comparable
3
3
promote the carbomethoxylation of the amine (entries 6 and
1
An analogous catalytic effect is clearly evident also when an
amine/DMC molar ratio higher than unity (RNH2/
DMC¼2.5–3 (mol/mol), Table 4) is used together with
9
8
, Table 1).
Whatever M(OTf) (M¼Sc or La) catalyst salt is used, the
catalytic amounts of M(OTf) (3–4% (mol/mol) vs DMC;
3
3
carbomethoxylation reaction requires strict anhydrous
conditions. We have ascertained that addition of water to
the reaction markedly inhibits the catalytic activity of both
M¼Sc or La).
The carbomethoxylation reaction is very selective. In all
cases (Tables 3 and 4), the metal triflate promotes the
carbamation of the amine in a selective way (h 100%).
M(OTf) salts (M¼Sc, La; Table 2).
3
In principle, water is expected to effectively compete with
2.2. Kinetic and mechanistic considerations
After addition of amine to the M(OTf) salt in DMC, the
3
Table 1. Carbomethoxylation of PhCH NH
Group 3 metal (La, Sc) salt at ambient temperature (20 8C)
2
2
with DMC in the presence of a
a
separation of poorly soluble metal species from the reaction
medium may occur. In only a few cases (entries 2 and 8,
Table 3; entries 3 and 9, Table 4), the reaction mixture
remains homogeneous throughout the catalytic run. These
features make it difficult to compare, for each amine, the
catalytic efficiency of the M(OTf)3 (M¼Sc, La) salts
quantitatively (as measured, for instance, by turnover-
numbers (TONs)). A better insight into this issue is provided
by the inspection of Figure 1 which shows the profile of
formation of RNHC(O)OMe (R¼benzyl, n-butyl, allyl, iso-
Entry
Metal salt
M (La, Sc)
(
Time (h)
Carbamate
b
yield (%)
mmol)
1
2
3
4
5
6
7
8
None
—
17
23.5
6
2
2
1
10
27
71
34
75
LaCl
LaCl
3
0.067
0.067
0.067
0.067
0.067
0.072
0.072
3
·7H
2
O
·7H
La(NO
La(OTf)
La(OTf)
Sc(OTf)
Sc(OTf)
3
)
3
2
O
4
3
0.5
24.0
0.7
20.9
3
3
3
butyl) carbamates in the presence of the M(OTf) (M¼Sc,
3
a
La) salts, under the experimental conditions reported in
Table 3. Curves (c) and (d) for (n-butyl)NHC(O)OMe and
(g) and (h) for (iso-butyl)NHC(O)OMe show that carbamate
To the used Sc or La salt in DMC, the amine was added. PhCH
.100 mL, 0.916 mmol; DMC: 1.0 mL, 11.87 mmol (in all the runs).
GC-yield versus the amine (internal standard: n-undecane (30 mL)).
2 2
NH :
0
b

M. Distaso, E. Quaranta / Tetrahedron 60 (2004) 1531–1539
Table 3. Carbomethoxylation of aliphatic amines RNH with DMC at ambient temperature (20 8C): catalytic effect of M(OTf)
1533
a
2
3
(M¼Sc, La) salts
b
Entry
R
RNH
2
(mmol)
DMC (mmol)
Sc(OTf)
3
(mmol)
La(OTf)
3
(mmol)
Time (h)
RNHC(O)OMe yield (%)
1
2
3
4
5
6
7
8
9
Benzyl
Benzyl
Benzyl
n-Butyl
n-Butyl
n-Butyl
Allyl
Allyl
Allyl
i-Butyl
i-Butyl
i-Butyl
0.916
0.916
0.916
0.908
0.908
0.908
0.868
0.868
0.868
0.897
0.897
0.897
11.87
11.87
11.87
11.87
11.87
11.87
11.87
11.87
11.87
11.87
11.87
11.87
0.0723
—
—
0.0680
—
—
0.0642
—
—
0.0670
—
—
—
20.9
24.0
17
24.8
24.8
20
22.5
25.4
26
25.0
78.3
25
75
71
2
79
69
15
76
77
3
0.0669
—
—
0.0699
—
—
0.0678
—
—
0.0695
—
1
1
1
0
1
2
70
58
c
7
a
b
c
3
To the M(OTf) salt in DMC, the amine and n-undecane (internal standard) were in sequence added.
GC-yield versus amine.
Carbamate yield was equal to 49% after a reaction time of 22.5 h.
Table 4. Aminolysis of DMC by aliphatic amines RNH
2
(excess), at ambient temperature (20 8C), in the presence of M(OTf)
3
(M¼Sc, La) salts
a
Entry
R
RNH
2
(mmol)
DMC (mmol)
Sc(OTf)
3
(mmol)
La(OTf)
3
(mmol)
Time (h)
RNHC(O)OMe yield (%)
1
2
3
4
5
6
7
8
9
Benzyl
Benzyl
Benzyl
Allyl
Allyl
Allyl
i-Butyl
i-Butyl
i-Butyl
4.58
4.58
4.58
5.04
5.35
5.35
6.85
4.68
4.88
1.78
1.78
1.78
1.78
1.78
1.66
1.78
1.78
1.78
—
—
—
0.0698
—
—
0.0665
—
—
24
21.2
48
24
4
4
24
24.3
23.5
23
82
83
43
83
69
59
86
76
0.0657
—
—
0.070
—
—
0.0657
—
0.0693
a
GC-yield versus DMC (internal standard: n-undecane).
formation is more efficient under Sc(OTf) catalysis. For
3
The higher catalytic activity of the Sc salt can be related
with the higher Lewis acidity of Sc(III) with respect to La
(
benzyl)NHC(O)OMe (curves (a) and (b)) and (allyl)NH-
2
1
˚
(III), as a result of their different ionic radii (0.89 A for
C(O)OMe (curves (e) and (f)) the curves of formation in the
presence of La(OTf) or Sc(OTf) almost overlap, although
3
þ
˚
3þ 22
Sc and 1.17 A for La ). The higher the acidity of the
metal centre, the higher the reactivity of the substrate
(DMC), which is more strongly activated towards the
nucleophilic attack by amine.
3
3
the reaction mixture remains homogeneous throughout the
reaction time in the former case (M¼La), while is
heterogeneous in the latter (M¼Sc), because of the
precipitation of poorly soluble Sc-derivatives. These
features suggest that Sc(OTf) is a more effective catalyst
3
than La(OTf) in this reaction.
3
The curves reported in Figure 1 indicate that, with the
exception of the system La(OTf) /iso-butylamine/DMC
2
0
3
Figure 1. Curves of formation (20 8C) of RNHC(O)OMe carbamate esters by carbomethoxylation of aliphatic primary amines RNH
2
with DMC (1.0 mL,
: 0.0723 mmol. (b) PhCH NH
: 0.908 mmol; La(OTf) : 0.0699 mmol.
: 0.0678 mmol. (g) (CH CHCH NH
3
: 0.0695 mmol. Carbamate yield was equal to 58.3% after a reaction time
1
1.87 mmol) in the presence of M(OTf)
.916 mmol; La(OTf) : 0.0669 mmol. (c) CH
vCHCH NH : 0.868 mmol; Sc(OTf)
.897 mmol; Sc(OTf) : 0.0670 mmol. (h) (CH
3
(M¼Sc, La). Experimental conditions: (a) PhCH
(CH NH : 0.908 mmol; Sc(OTf) : 0.0680 mmol. (d) CH
: 0.0642 mmol. (f) CH vCHCH NH : 0.868 mmol; La(OTf)
CHCH NH : 0.897 mmol; La(OTf)
2
NH
2
: 0.916 mmol; Sc(OTf)
3
2
2
:
0
3
3
2
)
3
2
3
3
(CH NH
2
)
3
2
3
(
e) CH
2
2
2
3
2
2
2
3
3
)
2
2
2
:
0
3
3
)
2
2
2
of 78.3 h.

1534
M. Distaso, E. Quaranta / Tetrahedron 60 (2004) 1531–1539
2
4
nol, as suggested in Eq. 2.
0
L MðOTfÞ þ xMeOH þ xRR NH
n
3
ð2Þ
0
!
LnMðOMeÞðOTfÞ32x þ xðRR NH ÞOTf
2
0
M¼Sc, La and L¼ligand, R ¼H, alkyl.
The reactivity described by Eq. 2 is not completely new,
as it has been documented in the literature and used for
the synthesis of rare-earth alkoxides, Ln(OR) , by reaction
3
of the corresponding chlorides, LnCl , with alcohols in the
3
2
5
presence of bases (Eq. 3).
Figure 2. Carbomethoxylation of PhCH
M(OTf)
addition of amine at the plateau. Experimental conditions: (a) La(OTf)
2 2
NH with DMC in the presence of
LnCl þ 3ROH þ 3NH ! LnðORÞ þ 3ðNH ÞCl
Ln¼rare-earth metal
ð3Þ
3
3
3
4
3
(M¼Sc, La) at ambient temperature (20 8C): effect of further
3
:
0
0
0
0
.0669 mmol, PhCH
.100 mL (0.916 mmol) of benzylamine were added. (b) Sc(OTf)
.0723 mmol, PhCH NH
.100 mL (0.916 mmol) of benzylamine were added.
2
NH
2
: 0.916 mmol, DMC: 11.87 mmol. After 24 h,
3
:
0
Ad hoc experiments allowed us to exclude that (RR NH )
2
2
2
: 0.916 mmol, DMC: 11.87 mmol. After 21 h,
OTf salts may play a significant role as carbomethoxylation
catalysts. In fact, as shown in Table 5 for the carbamation
of PhCH NH with DMC at 20 8C, (PhCH NH )OTf
(
curve (h), Fig. 1), a quite interesting initial conversion is
observed as the carbamate yield ranges between 50 and
5%, at ambient temperature, within a reaction time of 3 h.
Figure 2 shows that, for the system M(OTf) /PhCH NH /
2
2
2
3
(0.06585 g, 0.257 mmol; completely soluble in DMC
2
6
6
(1 mL)) exhibits only a modest catalytic activity, which
is, however, somewhat lower than that of the M(OTf)3
(M¼Sc, La) salts.
3
2
2
DMC (M¼Sc, La) at 20 8C, if amine is added to the reaction
mixture at the plateau, the reaction restarts with an
appreciable production of more carbamate ester. This
demonstrates that the catalyst is still active, although not
so effective as at the beginning. The restart of the reaction
upon addition of fresh amine indicates that the residual
unreacted amine may be in a form that is not prone to react
with DMC: the nucleophilicity of the amine must be
reduced in some way. Also, the diminished catalytic activity
is indicative of a modification of the catalyst which may
progressively deactivate by converting into a catalytically
less active species.
2.3. Influence of temperature
Benzylamine has been used for studying the influence of
temperature on the carbomethoxylation reaction. Table 6
summarizes the results obtained with Sc(OTf) as catalyst.
3
2
8
At 90 8C, the carbamation of the amine, albeit faster, takes
place less selectively than at room temperature (see entries 1
and 2, Table 6).
Entries 3 and 4 (Table 6) illustrate the results obtained at
90 8C under conditions different from those used in entry 2.
In entry 3, the use of a higher (vs entry 2) amount of the
In order to shed light on these issues, we have carried out a
complete analysis of the reaction solution. We have found
that the amine can undergo protonation and convert into the
amine (Sc(OTf) /amine¼3.1% vs 8.04% (mol/mol) in
3
þ
corresponding alkylammonium cation RNH , that is not
3
entry 2), without appreciably changing the analytical
reactive towards DMC and can be recovered at the end of
the reaction as alkylammonium triflate salt, (RNH )OTf.
concentration of the catalyst ([Sc(OTf) ]¼0.06 mol/L vs
3
0.07 mol/L in entry 2) results in a better carbamate yield, but
the selectivity is lower (95%), albeit still good. A marked
reduction of selectivity and yield is observed in entry 4,
where a significantly lower (vs entry 2) catalyst loading
3
This particular issue has been investigated in detail for
the system Sc(OTf) /PhCH NH /DMC (Sc/amine/DMCh
3
2
2
1
:13:172 (mol/mol)). IR monitoring of the reaction solution
revealed the formation of (PhCH NH )OTf (characteristic
is used with respect to both the amine (Sc(OTf) /amine¼
2
3
1
3
2
absorptions at 3258, 3166, 643 cm ) soon after (about
0–45 min) the reactants were mixed. The work-up of the
0.62% (mol/mol)) and DMC ([Sc(OTf) ]¼0.005 mol/L).
3
3
reaction mixture, at the end of the catalytic run, allowed to
isolate the salt (PhCH NH )OTf (1.80 mol of salt per mol of
Sc), that was characterized by IR and NMR spectroscopy.
Analogous trends are found when La(OTf)3 is used as
catalyst in place of Sc(OTf) (90 8C). Figure 3 shows the
curve of formation of PhCH NHC(O)OMe by carbometh-
2
2
3
3
2
3
oxylation of PhCH NH with DMC in the presence of
2
2
Most likely, the proton source is the coproduced metha-
La(OTf) , under conditions otherwise comparable with
3
Table 5. Carbomethoxylation of PhCH
2
NH
2
with DMC at ambient temperature (20 8C): (PhCH NH
2
3
)OTf vs M(OTf)
3
(M¼Sc, La) catalytic activity
a
Catalyst
PhCH
2
NH
2
(mmol)
DMC (mmol)
Catalyst/amine (mol/mol)%
Time (h)
PhCH
2
NHC(O)OMe yield (%)
None
(PhCH
Sc(OTf)
0.916
0.916
0.916
0.916
11.87
11.87
11.87
11.87
0
17
19
20.9
24.0
2
2
NH
3
)OTf
28
7.9
7.3
10
75
71
3
La(OTf)
3
a
GC-yield versus the amine (internal standard: n-undecane).

M. Distaso, E. Quaranta / Tetrahedron 60 (2004) 1531–1539
1535
Under the described conditions, aliphatic primary amines,
such as benzylamine, n-butylamine and allylamine, are
selectively (h 100%) converted into the corresponding
methylcarbamate esters in good yields (Table 7).
This study has been extended to secondary aliphatic amines,
such as morpholine and piperidine. At 20 8C, under the
conditions reported in Table 7, also these amines are very
selectively (h 100%) carbomethoxylated, but at a lower rate
than the primary ones. After ,24 h, in both cases, the
amount of unreacted amine was still close to 20%. The
carbamation of morpholine was carried out also at higher
temperature. At 65 8C (Sc/amine¼3.0% (mol/mol); DMC/
Sc¼76.0 (mol/mol)), as expected, a marked decrease in
selectivity is observed due to the appreciable side-formation
Figure 3. Carbomethoxylation of PhCH
of La(OTf) at 90 8C. Experimental conditions: La(OTf)
PhCH NH : 2.29 mmol, DMC: 11.87 mmol.
2
NH
2
with DMC in the presence
3
3
: 0.0681 mmol,
2
2
2
9
of N-methylmorpholine.
those used in entry 3, Table 6. After 9.5 h at 90 8C, a
carbamate yield close to 83% is obtained, with a selectivity
to the carbamate ester around 95%.
As for the fate of the catalyst, we have emphasized above
that, to some extent, Sc(III) precipitates during the reaction
in the form of unsoluble species that have been recovered at
3
0
2
.4. Synthetic applications
the end of the catalytic run by filtration. Unfortunately,
their poor solubility in common organic solvents precluded
any re-crystallization and in no case have we been able to
The carbomethoxylation of a few amines was carried out
at ambient temperature (20 8C) under conditions more
appealing from the synthetic point of view than those
employed in Table 3, by using a lower catalyst/amine molar
ratio (h 3% vs h 8% (mol/mol)). In order to realize a
higher concentration of both nucleophile and catalyst in the
reaction mixture, a markedly lower DMC/triflate salt molar
ratio (75–95 vs 160–185 (mol/mol)) was also used. We
3
1
isolate well defined compounds. When reused at 20 8C,
the crude precipitate still exhibits a catalytic activity.
However, this results in lower activity as compared to the
starting catalyst.
3. Conclusions
focused our attention on the use of Sc(OTf) as the catalyst,
3
because of its higher catalytic activity with respect to the
homologue La salt.
For the first time Group 3 metal salts have been employed
as catalysts for the carbamation of amines with dimethyl-
carbonate. Both Sc(OTf) and La(OTf) effectively promote
3
3
the carbomethoxylation of aliphatic amines with DMC at
20 8C to afford the corresponding carbamate esters with
Table 6. Carbomethoxylation of PhCH NH
2
2
with DMC in the presence of
Sc(OTf) under different experimental conditions
3
good yields and excellent selectivity (h 100%). Sc(OTf)
3
exhibits a higher catalytic activity than La(OTf) . The
a
b
3
Entry RNH
(
2
DMC Sc(OTf)
3
T
mmol) (mmol) (mmol) (8C) (h)
Time Yield
(%)
Selectivity
(%)
presence of water in the reaction medium inhibits the
catalytic activity of both triflate salts at ambient tempera-
ture. Temperature affects the selectivity of the carbo-
methoxylation reaction, being less selective at higher
temperature, because of the increased incidence of the
N-methylation processes.
1
2
3
4
0.916
0.916
2.29
11.87 0.0723
11.87 0.0737
11.87 0.0701
20 20.9
75
75
84
. 99.5
98
95
c
90
90
9.1
8.7
d
9.16
118.7
0.0569
90 27.4
57
89
a
Carbamate GC-yield vs the amine (internal standard: n-undecane).
b
Selectivity to carbamate ester. The observed side-products were
PhCH )N(Me)H and (PhCH )N(Me)
The reaction mixture was heated at 90 8C for 9.1 h and analyzed by GC.
Then, 0.100 mL (0.916 mmol) of PhCH NH were further added and the
(
2
2
2
.
c
4. Experimental
2
2
reaction mixture heated at 90 8C for 6 h longer. After this time, the overall
carbamate yield (vs the total amount of amine used) was 70% (95%
selectivity).
After the first 2 h, the carbamate yield was equal to 16% and selectivity
.99%. However, the selectivity decreased with time and, after 27.4 h, the
overall yield of N-alkylation products was close to 7%.
4
.1. General
d
Unless otherwise stated, all reactions and manipulations
were conducted under a dinitrogen atmosphere, by using
vacuum line techniques. All solvents were dried according
3
Table 7. Synthesis of methyl carbamates from amines and DMC in the presence of Sc(OTf) , at ambient temperature (20 8C)
Amine
Sc/amine (mol/mol)%
DMC/Sc (mol/mol)
Time (h)
RNHC(O)OMe isolated yield (%)
PhCH
2
NH
vCHCH
(CH NH
2
2
3.0
3.0
3.0
3.1
3.0
97.0
94.7
90.1
78.9
75.2
24
24
24
48
48
83
77
82
81
80
CH
CH
2
2 2
NH
3
2
)
3
Piperidine
Morpholine

1536
M. Distaso, E. Quaranta / Tetrahedron 60 (2004) 1531–1539
3
2
(Nujol, cm21): 3181, 3093 (s, br), 1617 (m), 1499, 1385,
1245 (vs), 1165 (s), 1115, 1056, 1032 (s), 967, 918, 865,
to literature methods and stored under N . DMC (Fluka)
2
˚
was dried over 5 A molecular sieves for 24 h, filtered,
distilled, and stored under N . The amines (Fluka or Aldrich
2
1
788, 749, 723, 699, 635, 585, 574, 515, 487. H NMR
(THF-d , 500.138 MHz): d 4.22 (s, 2H, CH ), 7.34–7.42
products) were dried over KOH, distilled, and stored under
N . M(OTf) (M¼Sc, La) salts (Fluka, Aldrich) were used
8
2
(m, 3H, Haromatic), 7.52 (m, 2H, Haromatic), 7.82 (br, 3H,
1
2
3
3
as received and manipulated under an inert gas atmosphere.
NH3). C NMR (THF-d , 125.760 MHz): d 44.39 (CH ),
8 2
1
(C
21.76 (q, CF , J ¼320.5 Hz), 129.67, 129.85, 134.52
)].
aromatic
3
CF
IR spectra were obtained with a Perkin Elmer 883
spectrophotometer or with a Perkin Elmer FTIR 1710
instrument. NMR spectra were run on a Varian XL-200 or a
The resulting solution was washed with H O, which
2
1
Bruker AM 500 instrument, as specified in the text. H and
1
C chemical shifts are in ppm versus TMS and referenced
extracted more (PhCH NH )OTf together with minor
2
3
3
amounts of carbamate ester. The organic solution was
dried (Na SO ) and concentrated in vacuo to give the pure
carbamate PhCH NHC(O)OMe (83%, mp: 65–67 8C).
to the solvent peak. GC–MS analyses were carried out with
a Shimadzu GC-17A linked to a Shimadzu GCMS-QP5050
selective mass detector (capillary column: Supelco MDN-
2
4
2
Anal. Calcd for C H NO : C, 65.45; H, 6.67; N, 8.47.
9
11
2
5S, 30 m£0.25 mm, 0.25 mm film thickness). GC analyses
were performed with a HP 5890 Series II gas-chromato-
Found: C, 65.55; H, 6.73; N, 8.40.
graph (capillary column: Heliflex AT-5, 30 m£0.25 mm,
4.3.2. Synthesis of CH vCHCH NHC(O)OMe by reac-
2
tion of CH vCHCH NH with DMC in the presence of
2 2 2
2
0
.25 mm film thickness).
Sc(OTf) . Allylamine (0.930 mL, 12.43 mmol) was added
3
4.2. Carbomethoxylation of PhCH NH with DMC:
influence of H O on the catalytic activity of the M(OTf)
to the solution of Sc(OTf) (0.18505 g, 0.376 mmol) in
3
2
2
DMC (3.0 mL, 35.60 mmol). The reaction mixture was
stirred at 20 8C for 24 h, diluted with diethylether (30 mL)
and filtered.
2
3
(
M5Sc, La) salts
To the solution of Sc(OTf) in DMC, or to the suspension
3
1
9
of La(OTf) in the same solvent, H O was added (see
2
The resulting solution was treated with H O, which
3
2
extracted allylammonium triflate [IR (Nujol, cm2 ): 3171
(vs, br), 1651 (m, sh), 1614 (m, br), 1505 (m), 1430, 1250
(vs), 1198, 1168 (s), 1130, 1032 (s), 991, 951, 876, 763, 645,
1
Table 2). Upon addition of PhCH NH to the resulting
2
2
homogeneous solutions, the fast separation of a poorly
soluble colorless solid was observed. The resulting mixture
was allowed to react at 20 8C and then analyzed by GC
1
582, 517. H (CD CN, 500.138 MHz): d 3.58 (dt, 2H, CH ,
3
2
3
4
(
Table 2).
JH–H¼6.29 Hz, J
¼1.3 Hz), 5.38 (dm, 1H, H ), 5.43
H–H
cis
(
dm, 1H, H
), 5.91 (ddt, 1H, CH vCH, J ¼10.34 Hz,
trans
2
cis
3
13
The separated solids, isolated by centrifugation after their
precipitation (30 min) or at the end of the catalytic run
Table 2), were found to contain Sc(III) or La(III)
according to the used M(OTf) salt) and evolved CO
upon acidolysis with diluted HCl. Moreover, their IR
spectra showed strong absorptions at 3350–3340, 1570–
Jtrans¼17.30 Hz, J
¼6.3 Hz), 6.51 (br, 3H, NH ).
C
H–H
3
(CD CN, 125.760 MHz): d 43.05 (C
3
), 119.08 (q, CF ,
3
allylic
3
3
1
(
J ¼320 Hz), 122.00 (H CvCH), 129.76 (CH vCH)]
CF
2
2
(
together with minor amounts of carbamate. The organic
phase was dried (Na SO ) and concentrated in vacuo to give
the pure carbamate CH vCHCH NHC(O)OMe (77%).
3
2
2
4
2
2
2
1
1500, 1345–1340 cm , consistent with the presence of a
3
carbamate group. The low solubility of these species in
Anal. Calcd for C H NO : C, 52.16; H, 7.88; N, 12.16.
5 9 2
Found: C, 52.10; H, 7.93; N, 12.10.
4
D O, where decomposition is also observed, and other
2
common organic solvents has precluded their purification
and full characterization.
4.3.3. Synthesis of CH (CH ) NHC(O)OMe by reaction
2 3
3
of CH (CH ) NH with DMC in the presence of
3
2 3
2
Sc(OTf) . n-Butylamine (1.30 mL, 13.18 mmol) was
3
4.3. Synthesis of carbamate methyl esters by aminolysis
of DMC in the presence of Sc(OTf) at ambient
temperature (20 8C)
added to the solution of Sc(OTf)3 (0.19445 g,
0.395 mmol) in DMC (3.0 mL, 35.60 mmol). The reaction
mixture was reacted at room temperature for 24 h, diluted
with diethylether (10 mL), and filtered. To the resulting
solution n-pentane (70 mL) was added. Upon cooling to
220 8C overnight, colorless needles of pure [(CH (CH ) -
3
1
13
Product yields were not optimized. The MS, IR, H and
NMR of PhCH NHC(O)OMe and CH vCHCH NHC
C
2
2
2
3
2 3
1
2a
(
O)OMe were identical with those of authentic samples.
NH ]OTf separated from the solution and were isolated by
3
filtration (0.07395 g, 0.331 mmol) [IR (Nujol, cm2 ): 3178
1
4.3.1. Synthesis of PhCH NHC(O)OMe by reaction of
PhCH NH with DMC in the presence of Sc(OTf)3.
Benzylamine (1.30 mL, 11.91 mmol) was added to the
solution of Sc(OTf)3 (0.18055 g, 0.367 mmol) in DMC
(vs, br), 1613 (m-s), 1514, 1248 (vs, br), 1170 (vs), 1037 (s),
1
2
914, 794, 762, 738, 641, 581, 517. H (CD CN, 200 MHz):
3
2
2
3
d 0.91 (t, 3H, CH3, JH–H¼7.23 Hz), 1.37 (m, 2H,
CH CH ), 1.59 (m, 2H, CH CH CH ), 2.93 (m, 2H,
3
2
3
2
2
1
3
(
3.0 mL, 35.60 mmol) and the reaction mixture was allowed
NCH ), 6.27 (br, 3H). C (CD CN, 125.760 MHz): d
2 3
to react for 24 h at ambient temperature. After filtration, the
mother solution and washing (DMC) liquors, collected
together, were concentrated in vacuo. Upon addition of
CH Cl (15 mL) and cooling to 0 8C, pure (PhCH NH )OTf
13.65 (CH ), 20.07 (CH CH ), 29.53 (CH CH CH ), 40.93
3 2 3 2 2 3
1
(NCH ), 122.58 (q, CF , J ¼320.7 Hz)].
2
3
CF
The solution was extracted with H O (15 mL) from which
2
2
2
2
3
separated and was isolated by filtration, washed with
CH Cl and dried in vacuo (0.13670 g, 0.531 mmol) [IR
residual amounts of [(CH (CH ) NH ]OTf were recovered
3
(as established by IR), but not further purified. From the
2 3
3
2
2

M. Distaso, E. Quaranta / Tetrahedron 60 (2004) 1531–1539
1537
organic solution, dried over Na SO and concentrated in
2
was reacted for 48 h at 20 8C, then diluted with diethylether
(30 mL) and cooled to 220 8C overnight. After filtration,
the solution was evaporated in vacuo, and the residue
chromatographed on silica gel with diethylether/n-hexane
(2:1, v/v) as eluent to give pure carbamate with 80% yield.
Anal. Calcd for C H NO : C, 49.65; H, 7.64; N, 9.64.
4
vacuo, pure carbamate CH (CH ) NHC(O)OMe was iso-
3
2 3
lated (82%). Anal. Calcd for C H NO : C, 54.94; H, 9.99;
6
13
2
N, 10.67. Found: C, 54.87; H, 10.07; N, 10.50. IR (neat,
1
2
cm ): 3338 (m-s, br), 2961, 2874, 1707 (vs), 1535 (vs),
458, 1381, 1260 (vs), 1193, 1142, 1113, 1057, 1025, 781.
1
6
11
3
1
21
H NMR (CDCl , 500.138 MHz): d 0.82 (t, 3H, CH ,
3
Found: C, 49.57; H, 7.72; N, 9.57. IR (neat, cm ): 2960,
2900, 2859, 1702 (vs), 1466, 1445, 1407, 1363, 1301, 1280,
1245, 1222 (vs), 1191, 1117, 1073, 1025, 958, 917, 851,
3
3
JH–H¼7.35 Hz), 1.24 (m, 2H, CH CH ), 1.38 (quintuplet,
2
3
2
H, CH CH CH , J¼7.3 Hz), 3.07 (quartet, 2H, NCH ,
2
2
3
2
1
3
1
J¼6.6 Hz), 3.55 (s, 3H, OCH ), 5.2 (br, 1H, NH). C NMR
800, 769, 656, 568, 524, 475. H NMR (CDCl , 200 MHz):
3
3
(
CDCl , 125.760 MHz): d 13.76 (CH ), 19.91 (CH CH ),
3
d 3.36 (m, 4H, CH –N–CH ), 3.56 (m, 4H, CH –O–CH ),
2
3
2
3
2
2
2
1
3
3
2.14 (CH CH CH ), 40.80 (NCH ), 51.91 (OCH ), 157.23
2
3.62 (s, 3H, CH3). C NMR (125.760 MHz, CDCl ): d
3
2
3
2
3
þz
(
C(O)O). MS (m/z): 131 (M ), 116, 102, 88, 76, 59, 44.
43.61 (CH –N–CH ), 52.34 (CH ), 66.07 (CH –O–CH ),
2
2
2
3
þz
2
155.32 (C(O)O). MS(m/z): 145 (M ), 130, 114, 100, 86, 70,
56, 42.
4
.3.4. Synthesis of 1-carbomethoxypiperidine by reac-
tion of piperidine with DMC in the presence of Sc(OTf)3.
To the solution of Sc(OTf)3 (0.17785 g, 0.361 mmol)
in DMC (2.4 mL, 28.51 mmol) piperidine (1.15 mL,
Formed morpholinium triflate could be isolated in a pure
form according to the experimental procedure reported
below. The reaction mixture (Sc(OTf) : 0.18570 g,
1
1.62 mmol) was added. The reaction mixture was stirred
for 48 h at ambient temperature, treated with diethylether
35 mL) and cooled to 220 8C. After filtration, the mother
3
0.377 mmol; DMC: 2.40 mL, 28.51 mmol; C H NO:
4
9
(
1.10 mL, 12.61 mmol), prepared as previously described
and stirred for 48 h at 20 8C, was filtered. The solution, after
addition of diethylether (60 mL), was cooled to 220 8C
overnight. The solid precipitated was isolated by filtration,
washed with diethylether, dried in vacuo and identified as
pure morpholinium triflate (0.15255 g, 0.643 mmol) [IR
liquor and washing ethereal solutions (2£10 mL), collected
together, were extracted with H O. The organic layer, dried
2
over Na SO , was concentrated in vacuo to give pure
2
4
carbamate with 81% yield. Anal. Calcd for C H NO : C,
2
7
13
5
IR (neat, cm ): 1702 (s), 1535, 1474, 1446, 1410, 1372,
8.72; H, 9.15; N, 9.78. Found: C, 58.65; H, 9.20; N, 9.70.
21
21
(Nujol, cm ): 3066, 1604, 1276 (br), 1197, 1165, 1107,
1031, 903, 876, 763, 723, 638, 591, 575, 518, 476, 440,
1
8
6
352, 1282, 1265, 1238, 1190, 1152, 1090, 1029, 947, 900,
1
1
54, 839, 791, 719. H NMR (CDCl , 200 MHz): d1.41 (m,
3
420. H NMR (CD CN, 200 MHz): d 3.18 ppm (m, 4H,
3
H, CH CH CH ), 3.26 (m, 4H, CH –N–CH ), 3.53 (s, 3H,
2
CH –N–CH ), 3.83 (m, 4H, CH –O–CH ), 6.8 (br, NH ).
2
2
2
2
2
2
2
2
2
1
3
13
OCH3). C NMR (CDCl , 125.760 MHz): d 24.44 and
3
C NMR (CD CN, 125.760 MHz): 44.81 ppm (CH –N–
3 2
CH ), 64.19 (CH –O–CH ), 121.78 (q, CF , JCF
3
320.4 Hz)]. The IR and NMR spectra reported above were
carried out on the aged product (stored under dinitrogen, for
1
2
5.33 (CH –CH –CH ), 44.45 (CH –N–CH ), 52.03
2
¼
2
2
2
2
2
2
2
þz
(
OCH ), 155.60 (C(O)O). MS (m/z): 143 (M ), 128, 102,
3
8
4, 70, 56, 42.
1
month, at ambient temperature) and were identical to
Formed piperidinium triflate could be isolated in a pure
form according to the following experimental procedure.
The reaction mixture (Sc(OTf) : 0.18450 g, 0.375 mmol;
those shown by a sample of morpholinium triflate prepared
from morpholine and triflic acid in ether at 20 8C. The IR
spectrum (Nujol) of the fresh product, registered soon after
the isolation (see above), shows absorptions at 3022, 1554,
3
DMC: 2.40 mL, 28.51 mmol; C H N: 1.15 mL,
5
11
1
1.62 mmol), prepared as previously described and stirred
1417, 1262 (vs), 1233, 1221, 1161, 1098, 1043, 884, 867,
760, 645, 587, 515, 431, 410 cm2
1
for 48 h at 20 8C, was filtered. The solution, after addition of
diethylether (60 mL), was cooled to 220 8C overnight. The
separated colorless solid was isolated by filtration, washed
with diethylether, dried in vacuo and identified as pure
piperidinium triflate (0.10170 g, 0.432 mmol) [IR (Nujol,
.
4.4. Isolation of (PhCH NH )(OTf) from the reaction of
3
2
MeOH with PhCH NH in the presence of Sc(OTf)
3
2
2
2
1
cm ): 3163 (br, vs), 1592 (s), 1480, 1435, 1318, 1239 (vs),
To a CH Cl (9 mL) solution of Sc(OTf)3 (0.22870 g,
2 2
1
6
158 (s), 1082, 1029, 953, 922, 872, 866, 816, 761, 722,
1
0.465 mmol) and MeOH (0.270 mL, 6.657 mmol) benzyl-
amine (0.155 mL, 1.420 mmol) was added and the resulting
suspension stirred at ambient temperature (20 8C) for 3 h.
After filtration, the mother solution and washing (THF)
liquors, collected together, were concentrated in vacuo.
Upon addition of n-pentane and cooling to 220 8C,
colorless crystals of (PhCH NH )(OTf) separated and
33, 576, 547. H NMR (CD CN, 200 MHz): d 1.74 (m, 2H,
3
CH CH CH ), 1.92 (m, 4H, CH CH CH ), 3.10 (t, 4H,
2
CH –N–CH , J
2
1
2
2
2
2
2
1
3
¼5.7 Hz), 6.6 (br). C NMR (CD CN,
2
H–H
3
25.760 MHz): d 22.31 and 22.98 (CH CH CH ), 45.87
2
2
2
1
(
CH –N–CH ), 121.79 (q, CF , J ¼320 Hz)].
2
2
3
CF
2
3
Upon treating the filtered solution with H O and concen-
2
were isolated by filtration (0.22580 g; 0:88 mmol;
molðRNH3ÞOTf=molSc ¼ 1:89).
trating in vacuo the aqueous layer, a solid residue (0.075 g;
not further purified) was obtained, that resulted to contain
more piperidinium triflate (as established by IR).
Acknowledgements
4.3.5. Synthesis of 1-carbomethoxymorpholine by reac-
tion of morpholine with DMC in the presence of
Financial support from Italian MIUR is gratefully acknowl-
edged. M.D. wishes to thank the MIUR (L488/92) for a
fellowship. The authors are indebted with Professor Michele
Aresta (University of Bari) for helpful suggestions.
Sc(OTf) . To the solution of Sc(OTf) (0.18655 g,
3
3
0
(
.379 mmol) in DMC (2.4 mL, 28.51 mmol) morpholine
1.10 mL, 12.61 mmol) was added. The reaction mixture

1538
M. Distaso, E. Quaranta / Tetrahedron 60 (2004) 1531–1539
14. (a) Fu, Z.-H.; Ono, Y. J. Mol. Catal. 1994, 91, 399. (b) Fu, Y.;
Baba, T.; Ono, Y. J. Catal. 2001, 197, 91.
References and notes
1
. Anastas, P. T.; Kirchoff, M. M. Acc. Chem. Res. 2002, 35, 686.
. Aresta, M.; Quaranta, E. ChemTech 1997, 27(3), 32 and
references therein.
15. (a) Aresta, M.; Dibenedetto, A.; Quaranta, E. Green Chem.
1999, 237. (b) Aresta, M.; Dibenedetto, A.; Quaranta, E.
Tetrahedron 1998, 54, 14145.
2
3
. Babad, H.; Zeiler, A. G. Chem. Rev. 1973, 73, 75.
. (a) Barthelemy, J. Lyon Pharm. 1986, 37(6), 297. (b) Wu,
T.-T.; Huang, J.; Arrington, N. D.; Dill, J. M. J. Agric. Food
Chem. 1987, 35, 817. (c) Kato, T.; Suzuki, K.; Takahashi, J.;
Kamashita, K. J. Pestic. Sci. 1984, 9, 489. (d) Rivetti, F.;
Romano, U.; Sasselli, M. G. U.S. Patent 4514339, 1985.
16. (a) Onoda, T.; Tano, K.; Hara, Y. JP 54163527, 1979.
(b) Romano, U.; Fornasari, G.; Di Gioacchino, S. DE 3202690,
1982. (c) Lissel, M.; Rohani-Dezfuli, A. R.; Vogt, G. J. Chem.
Res. (S) 1989, 312.
4
1
1
1
7. For a recent comprehensive review, see: Kobayashi, S.;
Sugiura, M.; Kitagawa, H.; Lam, W. W.-L. Chem. Rev. 2002,
1
02, 2227.
(
e) Green, T. W.; Wuts, P. G. M. Protective groups in organic
8. LaCl , LaCl ·7H O, and La(NO ) ·7H O resulted to be poorly
3 2 3 3 2
3
synthesis; 3rd ed. Wiley: New York, 1999; pp 503–550.
. Cenini, S.; Pizzetti, M.; Crotti, C. Aspects of homogeneous
catalysis; Ugo, R., Ed.; Riedel: Dordrecht, The Netherlands,
soluble in DMC (Table 1). No solubilization of the used salt
was observed upon subsequent addition of the amine.
5
6
7
9. Lanthanum triflate was not completely soluble in anhydrous
DMC. Addition of benzylamine (Table 1) to the DMC
suspension of La(OTf)3 caused the complete solubilization
of the salt. Sc(OTf)3 easily dissolved in anhydrous DMC
1998; Vol. 6, pp 97–108.
. Hagemann, C. Kolhensaure derivate. In Methoden der
organishen chemie; 4th ed., Houben-Weil, Ed.; Georg
Thieme: Stuttgart, 1983; p 159 Band E4.
(
Table 1), but a heterogeneous reaction mixture was obtained
upon subsequent addition of PhCH NH to the DMC solution
of the Sc salt (see later in the text).
. (a) Massi Mauri, M.; Romano, U.; Rivetti, F. Ing. Chim. Ital.
2
2
1985, 21(6), 6 and references cited therein. (b) Rivetti, F.
Comptes Rendus Acad. Sci., Series II: Chimie 2000, 3(6), 497
and references therein.
2
2
2
2
0. Analogous conclusions can be drawn also when an amine/
DMC molar ratio higher than 1 is used (Table 4).
1. Tsuruta, H.; Yamaguchi, K.; Imamoto, T. J. Chem. Soc.,
Chem. Commun. 1999, 1703.
8
9
. Aresta, M.; Berloco, C.; Quaranta, E. Tetrahedron 1995, 51,
8073.
. Kita, Y.; Haruta, J.; Yasuda, H.; Fukunaga, K.; Shirouchi, Y.;
2. Cotton, F. A.; Wilkinson, G. Advanced inorganic chemistry:
5
Tamura, Y. J. Org. Chem. 1982, 47, 2697.
th ed., Wiley: New York, 1988; p 973.
1
0. (a) Porta, F.; Cenini, S.; Pizzotti, M.; Crotti, C. Gazz. Chim.
Ital. 1985, 115, 275. (b) Garcia Deleon, R.; Kobayashi, A.;
Yamauchi, T.; Ooishi, J.; Baba, T.; Masaki, S.; Hiarata, F.
Appl. Catal. A: Gen. 2002, 225, 43. (c) Baba, T.; Fujiwara, M.;
Oosaku, A.; Kobayashi, A.; Deleon, R. G.; Ono, Y. Appl.
Catal. A: Gen. 2002, 227, 1. (d) Curini, M.; Epifano, F.;
Maltese, F.; Rosati, O. Tetrahedron Lett. 2002, 43, 4895.
3. The formation of amine triflate salts has been documented also
for amines other than benzylamine (see Section 4). The
spectroscopic features of the isolated salts fully agree with
those exhibited by authentic samples obtained by reacting the
amine (1 equiv.) with CF
4. In support of this, we note that, at 20 8C, a CH Cl solution of
3 3
SO H (1 equiv.) in diethylether.
2
2
2
Sc(OTf) and MeOH (added in excess vs Sc to dissolve the
3
(
e) Baba, T.; Ono, Y. JP 089435, 2001. (f) Smith, R. C.;
metal triflate salt in the solvent used) immediately reacted with
Hunns, J. C. B. WO 9856758, 1998. (g) Shimazaki, Y.;
Kambe, N.; Sotozono, M. JP 07328435, 1995. (h) Shimazaki,
Y.; Kambe, N.; Sotozono, M. JP 07330708, 1995.
2 3
benzylamine to afford (PhCH NH )(OTf) (see Section 4). In
good agreement with what reported above, only two of the
three used equivalents of benzylamine were protonated, as
demonstrated by the fact that the moles of isolated
(
i) Calderoni, C.; Mizia, F.; Rivetti, F.; Romano, U. EP
3
7
91473, 1990. (j) Bosetti, A.; Cesti, P.; Calderazzo, F. EP
52413, 1997. (k) Gurgiolo, A. E. US 4268684, 1981.
(
2 3
PhCH NH )(OTf) salt per mole of Sc were close to 2
(
mol(RNH3)OTf/mol ¼1.89). Work is in progress to purify and
Sc
(
(
l) Onoda, T.; Tano, K.; Hara, Y. JP 55004316, 1980.
m) Romano, U.; Tesei, R. DE 2714540, 1977.
full characterize the very hygroscopic scandium derivative
that co-precipitated with (PhCH NH )(OTf) upon addition
2
3
1
1. (a) Vauthey, I.; Valot, F.; Gozzi, C.; Fache, F.; Lemaire, M.
Tetrahedron Lett. 2000, 41, 6347. (b) Gupte, S. P.; Shivarcar,
A. B.; Chaudari, R. V. J. Chem. Soc., Chem. Commun. 2001,
21
of the amine. IR (Nujol, cm ): 1331 (vs, OTf) and 1310 (s,
shoulder, OTf), 1238 (s, shoulder, OTf), 1212 (vs, OTf) and
1
195 (s, shoulder), 1044 (vs, C–O) and 1030 (s, shoulder,
2
620. (c) Carloni, S.; De Vos, D. E.; Jacobs, P. A.; Maggi, R.;
OTf), 639 (s, OTf). The IR spectrum in hexachlorobutadiene
showed medium–weak absorptions at 2942, 2833 and
Sartori, G. J. Catal. 2002, 205, 199. (d) Sima, T.; Guo, S.; Shi,
F.; Deng, Y. Tetrahedron Lett. 2002, 43, 8145. (e) Orsat, B.;
Alper, P. B.; Moree, W.; Mak, C.-P.; Wong, C.-H. J. Am.
Chem. Soc. 1996, 118, 712. (f) Hacking, M. A. P. J.; van
Rantwijk, F.; Sheldon, R. A. J. Mol. Catal. B: Enzym. 2000, 9,
21
463 cm consistent with the presence of methoxo-groups.
25
1
2
5. (a) Turevskaya, E. P.; Belokon, A. I.; Starikova, Z. A.;
Yanovsky, A. I.; Kirushenkov, E. N.; Turova, N. Ya.
Polyhedron 2000, 19, 705. (b) Mehrotra, R. C.; Batwara,
J. M. Inorg. Chem. 1970, 9, 2505. (c) Funk, H.; Kohler, B. Z.
Anorg. Allg. Chem. 1963, 325, 67.
2
01.
2. (a) Aresta, M.; Quaranta, E. Tetrahedron 1991, 47, 9489.
b) Aresta, M.; Dibenedetto, A.; Quaranta, E.; Boscolo, M.;
1
1
(
26. This result is reminiscent of the modest catalytic effect played
by pirrolidinium ion, when added as perchlorate salt, in the
aminolysis of phenyl or p-chlorophenyl p-nitrobenzoate by
Larsson, R. J. Mol. Catal. 2001, 174, 7. (c) See also Selva, M.;
Tundo, P.; Perosa, A. Tetrahedron Lett. 2002, 43, 1217.
3. (a) Brill, W. F. DE 2160111, 1972. (b) Cong, J.-S.; Xue, W.;
Zhao, X.-Q.; Wang, Y.-J. Hebei Gongye Daxue Xuebao 2001,
2
7
pirrolidine.
27. Menger, F. A.; Smith, J. N. J. Am. Chem. Soc. 1972, 94, 3824.
30, 32. Chem. Abstr. 135, 228449. (c) Baba, T.; Kobayashi, A.;
28. At 90 8C, in the presence of Sc(OTf) , the reaction mixture,
3
Yamauchi, T.; Tanaka, H.; Aso, S.; Inomata, M.; Kawanami,
initially heterogeneous, became homogeneous within 1.5 h.
29. The formation of N-methylmorpholine was confirmed by GC
Y. Catal. Lett. 2002, 82, 193.

M. Distaso, E. Quaranta / Tetrahedron 60 (2004) 1531–1539
1539
þz
and GC–MS (m/z: 101 (M ), 87, 57, 42) analyses. After 8 h at
5 8C, the selectivity (determined by GC) of the carbo-
methoxylation process was equal to 92% and decreased to
7% after 23 h.
most probably weakly coordinated to Scandium (as the low-
frequency shift suggests). Accordingly, the intensity of the
latter band markedly reduces upon washing the crude
precipitate with DMC. Moreover, the GC–MS analysis of
the DMC washing solution shows the presence of carbamate
ester, that is further confirmed, by IR spectroscopy, on the
residue of the DMC solution after evaporation of solvent
6
8
3
3
0. Minor amounts of Scandium (III) remain in solution and can
be recovered, together with residual amounts of alkyl-
ammonium triflate, by means of extractions with water
2
1
(
see Section 4).
(band at approximately 1700 cm (see Section 4) due to
nCvO in free carbamate esters).
32. Perrin, D. D.; Armarego, W. L. F.; Perrin, D. R. Purification of
laboratory chemicals; Pergamon: Oxford, 1986.
1. The IR spectra of the crude precipitates shows some common
features, independently from the used amine. In all cases, an
2
1
intense absorption is found between 1069 and 1056 cm , that
may be suggestive of metal-bonded-methoxo-groups. Strong
bands, due to triflate anion, are located at 1300–1200, 1180–
33. Feigl, F.; Anger, V. Spot texts in inorganic analysis; 6th ed.,
Elsevier: Amsterdam, 1972; pp 125 and 407.
2
1
1
170, 1031 and 639 cm . A medium–strong band is also
1
34. (a) Chisolm, M. H.; Extine, M. W. J. Am. Chem. Soc. 1977, 99,
782. (b) Aresta, M.; Dibenedetto, A.; Quaranta, E. J. Chem.
Soc., Dalton Trans. 1995, 3359.
2
observed between 1665 and 1675 cm , which we tentatively
assign to the carbonyl stretching of carbamate ester molecules,